1 00:00:05,896 --> 00:00:10,468 SO WHAT I'D LIKE TO DO IS 2 00:00:10,468 --> 00:00:12,303 WELCOME TO YOU THE FOURTH ANNUAL 3 00:00:12,303 --> 00:00:19,010 SYN BIOMEETING I'M JEMONT CHEN. 4 00:00:19,010 --> 00:00:20,811 I'M GLAD WE'RE ABLE TO HAVE THIS 5 00:00:20,811 --> 00:00:23,280 IN PERSON AND I LOOK FORWARD TO 6 00:00:23,280 --> 00:00:25,316 THE DISCUSSION WE'RE GOING HAVE 7 00:00:25,316 --> 00:00:27,251 ON THE STAGE, AT LUNCH, AT 8 00:00:27,251 --> 00:00:27,885 COFFEE BREAKS FOR THE NEXT TWO 9 00:00:27,885 --> 00:00:31,055 DAYS. 10 00:00:31,055 --> 00:00:35,660 TO START IT'S MY PLEASURE TO 11 00:00:35,660 --> 00:00:39,030 INTRODUCE DR. DAVID T. GEORGE. 12 00:00:39,030 --> 00:00:42,299 HE HAS 25 YEARS AS OF SERVICE AT 13 00:00:42,299 --> 00:00:44,468 THE NATIONAL INSTITUTES OF 14 00:00:44,468 --> 00:00:48,639 HEALTH AND POINTED THE DIRECTOR 15 00:00:48,639 --> 00:00:50,174 FOR NIBIB OVERSEEING PROGRAM 16 00:00:50,174 --> 00:00:53,344 DIVISIONS AND BIO ENGINEERING 17 00:00:53,344 --> 00:00:55,346 AND INFORMATICS TRAINING AND 18 00:00:55,346 --> 00:00:58,749 SMALL BUSINESS. 19 00:00:58,749 --> 00:01:04,021 DR. GEORGE FIRST JOINED NIBIB IN 20 00:01:10,394 --> 00:01:11,796 2002 AND APPOINTED ASSOCIATE 21 00:01:11,796 --> 00:01:14,632 DIRECTOR IN 2015 RESPONSIBLE FOR 22 00:01:14,632 --> 00:01:15,833 THE NIBIB NATIONAL ADVISORY 23 00:01:15,833 --> 00:01:17,201 COUNCIL OFFICE OF GRANTS 24 00:01:17,201 --> 00:01:19,470 MANAGEMENT AND SCIENTIFIC REVIEW 25 00:01:19,470 --> 00:01:21,305 AND COMMITTEE MANAGEMENT 26 00:01:21,305 --> 00:01:21,605 ACTIVITIES. 27 00:01:21,605 --> 00:01:25,609 IT'S MY PLEASURE TO WELCOME 28 00:01:25,609 --> 00:01:27,378 DR. GEORGE TO GIVE US OUR 29 00:01:27,378 --> 00:01:29,313 INTRODUCTORY TALK. 30 00:01:29,313 --> 00:01:39,490 THANK YOU. 31 00:01:42,226 --> 00:01:52,536 >> THANK YOU, JEMONT. 32 00:01:52,903 --> 00:01:55,473 I DIDN'T REALIZE JEMONT WAS 33 00:01:55,473 --> 00:01:57,975 GOING TO DO THAT AND I GUESS I'D 34 00:01:57,975 --> 00:02:00,444 BEEN AROUND AT NIBIB. 35 00:02:00,444 --> 00:02:02,780 AS JEMONT MENTIONED I'M THE 36 00:02:02,780 --> 00:02:03,314 ASSOCIATE DIRECTOR FOR 37 00:02:03,314 --> 00:02:04,648 EXTRAMURAL SCIENCE PROGRAM. 38 00:02:04,648 --> 00:02:07,218 I'M EXCITED TO WELCOME YOU HERE 39 00:02:07,218 --> 00:02:10,054 IN PERSON FOR THE FOURTH ANNUAL, 40 00:02:10,054 --> 00:02:13,290 WE USE THE WORD ANNUAL SLIGHTLY 41 00:02:13,290 --> 00:02:17,828 LIBERALLY WITH COVID MODIFYING 42 00:02:17,828 --> 00:02:24,769 THE EVENT OF THE FOURTH NIH 43 00:02:24,769 --> 00:02:25,436 SYNTHETIC BIOLOGY CONSORTIUM 44 00:02:25,436 --> 00:02:29,140 MEETING SO HAPPY TO HOLD IT IN 45 00:02:29,140 --> 00:02:29,707 PERSON FOR THE FIRST TIME 46 00:02:29,707 --> 00:02:30,141 SCIENCE 2019. 47 00:02:30,141 --> 00:02:34,145 THE FOCUS OF THIS YEAR'S MEETING 48 00:02:34,145 --> 00:02:35,112 IS BIO MANUFACTURING AND 49 00:02:35,112 --> 00:02:36,580 SYNTHETIC BIOLOGY. 50 00:02:36,580 --> 00:02:39,483 A TIMELY TOPIC FOR THE COMMUNITY 51 00:02:39,483 --> 00:02:41,185 GATHERED HERE. 52 00:02:41,185 --> 00:02:43,754 THE SPEAKERS AS YOU SEE HERE ARE 53 00:02:43,754 --> 00:02:44,889 WELL RECOGNIZED FROM THE 54 00:02:44,889 --> 00:02:45,790 SYNTHETIC BIOLOGY COMMUNITY. 55 00:02:45,790 --> 00:02:47,091 THEY REPRESENT A VARIETY OF 56 00:02:47,091 --> 00:02:50,995 RESEARCH AREAS AND TODAY WE'LL 57 00:02:50,995 --> 00:02:54,231 BE DISCUSSING ROLES IN BIO 58 00:02:54,231 --> 00:02:55,332 MANUFACTURING RELEVANT TO 59 00:02:55,332 --> 00:02:57,768 SYNTHETIC BIOLOGY. 60 00:02:57,768 --> 00:02:58,669 THEY'RE ALSO REPRESENTATIVE 61 00:02:58,669 --> 00:03:00,671 EXPERTISE FROM INDUSTRY, 62 00:03:00,671 --> 00:03:01,172 ACADEMIA AND GOVERNMENT. 63 00:03:01,172 --> 00:03:03,607 SO I'D LIKE TO WELCOME THE 64 00:03:03,607 --> 00:03:04,875 INVITED SPEAKERS, THE LIGHTNING 65 00:03:04,875 --> 00:03:07,678 SPEAKERS AND THE POSTER 66 00:03:07,678 --> 00:03:12,283 PRESENTERS TODAY. 67 00:03:12,283 --> 00:03:15,186 SO IN TERMS OF BACKGROUND, THIS 68 00:03:15,186 --> 00:03:17,087 AUDIENCE SURELY DOESN'T NEED AN 69 00:03:17,087 --> 00:03:18,989 INTRODUCTION TO SYNTHETIC 70 00:03:18,989 --> 00:03:22,760 BIOLOGY ESPECIALLY FROM A 71 00:03:22,760 --> 00:03:24,461 NON-SYNTHETIC BIOLOGIST BUT TO 72 00:03:24,461 --> 00:03:26,664 REFLECT ON THE HISTORY OF FIELD. 73 00:03:26,664 --> 00:03:31,468 IN 2010, THERE WAS AN ARTICLE IN 74 00:03:31,468 --> 00:03:36,774 NATURAL A NEWS FEATURE ENTITLED 75 00:03:36,774 --> 00:03:43,113 FIVE HARD TRUTHS FOR SYNTHETIC 76 00:03:43,113 --> 00:03:44,615 BIOLOGY TO BECOME A VIABLE 77 00:03:44,615 --> 00:03:45,683 PROCESS IN DEVELOPING FUTURE 78 00:03:45,683 --> 00:03:47,051 PRODUCTS, TOOLS AND 79 00:03:47,051 --> 00:03:48,719 APPLICATIONS. 80 00:03:48,719 --> 00:03:50,354 SINCE THIS PUBLICATION 13 YEARS 81 00:03:50,354 --> 00:03:56,560 LATER, THE RESEARCH DONE BY YOU 82 00:03:56,560 --> 00:03:57,328 THE SYNTHETIC BIOLOGY COMMUNITY 83 00:03:57,328 --> 00:04:01,999 HAVE ADDRESSED AREAS AND 84 00:04:01,999 --> 00:04:06,537 UNPREDICTABLE CIRCUITRY AND 85 00:04:06,537 --> 00:04:08,472 INCOMPATIBLE PARTS AND 86 00:04:08,472 --> 00:04:12,142 VARIABILITY AND CHRIS VOIGT HAD 87 00:04:12,142 --> 00:04:14,178 AN ARTICLE IN NATURE 88 00:04:14,178 --> 00:04:16,080 COMMUNICATIONS DESCRIBING SIX 89 00:04:16,080 --> 00:04:17,181 SYNTHETIC BIOLOGY-BASED PRODUCTS 90 00:04:17,181 --> 00:04:22,519 AVAILABLE IN 2020, A MERE 10 91 00:04:22,519 --> 00:04:25,522 YEARS AFTER CROIX ARTICLE AND A 92 00:04:25,522 --> 00:04:28,792 BIOLOGICAL RATHER THAN CHEMICAL 93 00:04:28,792 --> 00:04:31,061 NITROGEN FERTILIZER COMPATIBLE 94 00:04:31,061 --> 00:04:34,832 WITH CROPS AND ENVIRONMENTALLY 95 00:04:34,832 --> 00:04:39,169 SAFER THAN CHEMICAL NITROGEN 96 00:04:39,169 --> 00:04:42,306 FERTILIZER AND A DIRECTED 97 00:04:42,306 --> 00:04:45,309 EVOLUTION TREATMENT AND A 98 00:04:45,309 --> 00:04:47,611 SHINING EXAMPLE OF SYNTHETIC 99 00:04:47,611 --> 00:04:52,283 BIOLOGY WITH CAR T CELL 100 00:04:52,283 --> 00:04:57,421 IMMUNOTHERAPY FROM GENETICALLY 101 00:04:57,421 --> 00:05:03,060 MODIFIED T CELLS TO ADDRESS 102 00:05:03,060 --> 00:05:05,729 MALIGNANCY AND THESE SHOWCASE 103 00:05:05,729 --> 00:05:07,665 WHAT SYNTHETIC BIOLOGY CAN 104 00:05:07,665 --> 00:05:09,767 ACCOMPLISH IN THE AREAS OF 105 00:05:09,767 --> 00:05:13,304 AGRICULTURE, FOOD, MATERIALS, 106 00:05:13,304 --> 00:05:17,675 AND MEDICINE. 107 00:05:17,675 --> 00:05:18,642 HAVING SEEN GREAT PROGRESS, WHAT 108 00:05:18,642 --> 00:05:22,079 WILL THE FUTURE HOLD, IF WE HOLD 109 00:05:22,079 --> 00:05:24,982 THIS MEETING IN 2036 IN 13 YEARS 110 00:05:24,982 --> 00:05:29,954 WE'LL SEE A LONGER LIST OF 111 00:05:29,954 --> 00:05:32,456 ACCOMPLISHMENTS WHAT'S AN IDEA 112 00:05:32,456 --> 00:05:35,426 BEING TRANSLATED TO PRODUCTS IN 113 00:05:35,426 --> 00:05:37,127 THE FUTURE. 114 00:05:37,127 --> 00:05:43,834 SO GETTING BACK TO THE THEME OF 115 00:05:43,834 --> 00:05:45,302 THIS MEETING, BIO MANUFACTURING 116 00:05:45,302 --> 00:05:47,705 AND THE REASON IT'S IMPORTANT IS 117 00:05:47,705 --> 00:05:48,639 MANUFACTURING PROCESS IS 118 00:05:48,639 --> 00:05:50,574 CRITICAL AT ALL RESEARCH 119 00:05:50,574 --> 00:05:51,508 PRODUCTION SCALES. 120 00:05:51,508 --> 00:05:55,245 THE TRANSLATION FROM LAB SCALE 121 00:05:55,245 --> 00:05:55,879 MANUFACTURING TO INTERMEDIATE 122 00:05:55,879 --> 00:05:56,747 SCALE TO COMMERCIAL PRODUCTION 123 00:05:56,747 --> 00:05:58,182 IS NOT AN EASY ONE AND THERE'S 124 00:05:58,182 --> 00:06:03,087 CRITICAL CHALLENGE TO OVERCOME. 125 00:06:03,087 --> 00:06:04,421 BIO MANUFACTURING NEEDS TO BE 126 00:06:04,421 --> 00:06:07,191 REPEATABLE AND RELIABLE AND 127 00:06:07,191 --> 00:06:09,994 ACCURATE TO RELY ON SYNTHETIC 128 00:06:09,994 --> 00:06:13,097 BIOLOGY TOOLS AND TECHNIQUES TO 129 00:06:13,097 --> 00:06:18,068 BE TRUSTED STEPS IN THE 130 00:06:18,068 --> 00:06:24,508 MANUFACTURING PROCESS. 131 00:06:24,508 --> 00:06:27,945 IT WAS CALLED OUT ON ADVANCING 132 00:06:27,945 --> 00:06:28,679 BIO TECHNOLOGY AND BIO 133 00:06:28,679 --> 00:06:31,749 MANUFACTURING INNOVATION AND THE 134 00:06:31,749 --> 00:06:35,019 EXECUTIVE ORDER REQUESTED HHS 135 00:06:35,019 --> 00:06:38,055 FOR A REPORT ASSESSING HOW TO 136 00:06:38,055 --> 00:06:39,423 USE BIO MANUFACTURING AND BIO 137 00:06:39,423 --> 00:06:41,392 TECHNOLOGY TO REDUCE THE OVER 138 00:06:41,392 --> 00:06:45,562 ALL BURDEN OF DISEASE AND REDUCE 139 00:06:45,562 --> 00:06:49,500 HEALTH OUTCOMES. 140 00:06:49,500 --> 00:06:58,375 AND IT'S LED BY LOUSA RUSSELL 141 00:06:58,375 --> 00:07:00,844 CONTRIBUTED TO THE OUTLYING FIVE 142 00:07:00,844 --> 00:07:03,447 THEMES AND ACCESSIBLE MONITORING 143 00:07:03,447 --> 00:07:05,682 AND BIO MEDICINE AND CELL-BASED 144 00:07:05,682 --> 00:07:09,219 THERAP , A.I. DRIVEN BIO 145 00:07:09,219 --> 00:07:10,788 PRODUCTION OF THERAPIES AND 146 00:07:10,788 --> 00:07:12,856 ADVANCED TECHNIQUES OF GENE 147 00:07:12,856 --> 00:07:15,926 THERAPY AND OUTLINES BOLD GOALS 148 00:07:15,926 --> 00:07:17,227 UNDER EACH THEME. 149 00:07:17,227 --> 00:07:20,097 THE BIO MANUFACTURING ALSO 150 00:07:20,097 --> 00:07:25,803 COMPLIMENTS THE THEMES THE 151 00:07:25,803 --> 00:07:27,938 CONSORTIUM IS ADDRESSING 152 00:07:27,938 --> 00:07:28,939 CHALLENGES IN THE BIOLOGY FIELD 153 00:07:28,939 --> 00:07:31,642 FOR BIO MEDICAL APPLICATIONS. 154 00:07:31,642 --> 00:07:33,710 HERE LISTS THE PAST CONSORTIUM 155 00:07:33,710 --> 00:07:35,412 MEETING THE 2019 WAS THE 156 00:07:35,412 --> 00:07:37,047 INAUGURAL ONE. 157 00:07:37,047 --> 00:07:39,249 2020 IS WHAT IS NO LONGER ANNUAL 158 00:07:39,249 --> 00:07:42,319 AS MANY KNOW WAS CANCELED DUE TO 159 00:07:42,319 --> 00:07:42,519 COVID. 160 00:07:42,519 --> 00:07:44,321 MOVING THROUGH CANCER 161 00:07:44,321 --> 00:07:46,356 APPLICATIONS, CONTROL THEORY, 162 00:07:46,356 --> 00:07:51,595 THIS YEAR BIO MANUFACTURING AND 163 00:07:51,595 --> 00:07:54,298 NEXT YEAR THE NEXT CRITICAL 164 00:07:54,298 --> 00:07:55,432 CHALLENGE IN SYNTHETIC BIOLOGY. 165 00:07:55,432 --> 00:07:59,136 JUST TO GIVE A BRIEF HISTORY OF 166 00:07:59,136 --> 00:08:00,571 THE SYNTHETIC BIOLOGY 167 00:08:00,571 --> 00:08:01,238 CONSORTIUM. 168 00:08:01,238 --> 00:08:03,006 IT WAS FORMED IN 2018 DUE TO A 169 00:08:03,006 --> 00:08:04,541 GROWING INTEREST AT THE TIME. 170 00:08:04,541 --> 00:08:05,342 IT WASN'T CALLED SYNTHETIC 171 00:08:05,342 --> 00:08:07,678 BIOLOGY AT THE TIME. 172 00:08:07,678 --> 00:08:12,349 AS OF NOW THERE'S 12 I.C.s 173 00:08:12,349 --> 00:08:15,319 PARTICIPATING IN THE CONSORTIUM. 174 00:08:15,319 --> 00:08:18,222 THE NAME TAGS OF THOSE ARE MARK. 175 00:08:18,222 --> 00:08:20,557 FOR THOSE YOU HAVEN'T MET REACH 176 00:08:20,557 --> 00:08:24,461 OUT AND HAVE CONVERSATIONS. 177 00:08:24,461 --> 00:08:26,196 THIS LIST HERE SHOWS HIGHLIGHTS 178 00:08:26,196 --> 00:08:27,598 OF SOME OF THE DIFFERENT 179 00:08:27,598 --> 00:08:30,567 WEBSITES FROM THE CONSORTIUM 180 00:08:30,567 --> 00:08:31,535 MEMBERS ON THE TOP RIGHT AND 181 00:08:31,535 --> 00:08:34,138 NIBIB HAS A LIST OF THE MEMBERS 182 00:08:34,138 --> 00:08:36,707 AND THERE'S EXAMPLES FROM NCI 183 00:08:36,707 --> 00:08:41,245 AND HEART, LUNG AND BLOOD AND 184 00:08:41,245 --> 00:08:41,645 NHTRI. 185 00:08:41,645 --> 00:08:42,980 AND JUST TO GIVE A QUICK 186 00:08:42,980 --> 00:08:46,250 OVERVIEW OF THE FUNDING ACTIVITY 187 00:08:46,250 --> 00:08:49,153 OF THE CONSORTIUM ITSELF AND I 188 00:08:49,153 --> 00:08:51,288 WANT TO SAY THIS DOESN'T 189 00:08:51,288 --> 00:08:55,626 REPRESENT 100% OF THE FUNDING AT 190 00:08:55,626 --> 00:08:57,394 NIH BUT THE SPECIFIC INITIATIVES 191 00:08:57,394 --> 00:08:58,695 THE CONSORTIUM MEMBERS HAVE BEEN 192 00:08:58,695 --> 00:08:59,296 WORKING ON. 193 00:08:59,296 --> 00:09:01,798 THIS IS THE TIP OF THE ICEBERG 194 00:09:01,798 --> 00:09:02,866 BUT SOMETHING WE CAN REPORT WITH 195 00:09:02,866 --> 00:09:10,407 PUBLIC DATA AT THE MOMENT. 196 00:09:10,407 --> 00:09:12,142 STARTING WITH 2017 THEY ISSUED 197 00:09:12,142 --> 00:09:14,044 THE FIRST PROGRAM ANNOUNCEMENT 198 00:09:14,044 --> 00:09:17,281 AND STARTED FUNDING IN 2018. 199 00:09:17,281 --> 00:09:18,882 THERE'S A LOT OF MINUTIA IN HERE 200 00:09:18,882 --> 00:09:22,119 SO TAKE IT AS A RESOURCE BUT THE 201 00:09:22,119 --> 00:09:24,521 KEY POINT HERE IS THAT THERE WAS 202 00:09:24,521 --> 00:09:26,990 A PROGRAM ANNOUNCEMENT AND THEN 203 00:09:26,990 --> 00:09:27,791 IT BECAME NOTICE OF SPECIAL 204 00:09:27,791 --> 00:09:32,095 INTEREST WHICH IS A DIFFERENT 205 00:09:32,095 --> 00:09:33,330 WAY THAT NIH DEVELOPED AND 206 00:09:33,330 --> 00:09:36,266 SUPPOSED TO BE EQUIVALENT TO A 207 00:09:36,266 --> 00:09:36,667 PROGRAM ANNOUNCE 208 00:09:36,667 --> 00:09:38,602 THE AND INITIATIVES THAT EXPRESS 209 00:09:38,602 --> 00:09:41,338 A CONTINUOUS INTEREST ON PART OF 210 00:09:41,338 --> 00:09:43,707 THE CONSORTIA MEMBERS ON 211 00:09:43,707 --> 00:09:45,309 SYNTHETIC BIOLOGY AND THE 212 00:09:45,309 --> 00:09:47,077 RESULTING AWARDS FROM IT IN 213 00:09:47,077 --> 00:09:48,378 MILLIONS OF DOLLARS. 214 00:09:48,378 --> 00:09:51,114 THERE WAS AN INITIATIVE WITH NCI 215 00:09:51,114 --> 00:09:53,050 AND NIBIB THAT HAD A SINGLE DUE 216 00:09:53,050 --> 00:09:54,251 DATE AND THIS IS SHOWN HERE. 217 00:09:54,251 --> 00:09:57,888 SO YOU CAN SEE THERE'S BEEN A 218 00:09:57,888 --> 00:10:01,325 GROWING INTEREST IN FUNDING 219 00:10:01,325 --> 00:10:02,125 APPLICATIONS IN SYNTHETIC 220 00:10:02,125 --> 00:10:02,793 BIOLOGY AREA. 221 00:10:02,793 --> 00:10:05,929 AND THIS SHOWS THE AWARDS BY 222 00:10:05,929 --> 00:10:06,263 INSTITUTE. 223 00:10:06,263 --> 00:10:12,302 IT LOOKS LIKE MY LABELS HAVE 224 00:10:12,302 --> 00:10:12,703 DISAPPEARED. 225 00:10:12,703 --> 00:10:14,805 THIS UNDERWRITE IS NIBIB AND 226 00:10:14,805 --> 00:10:16,907 THIS IS NCI. 227 00:10:16,907 --> 00:10:19,509 THERE'S CUSTING AND PASTING -- 228 00:10:19,509 --> 00:10:23,547 CUTTING AND PASTING FAILURE ON 229 00:10:23,547 --> 00:10:26,984 MY PART. 230 00:10:26,984 --> 00:10:30,520 AND EARLY ON THERE WERE THREE I 231 00:10:30,520 --> 00:10:31,688 THINK INSTITUTES WERE INVOLVED 232 00:10:31,688 --> 00:10:35,359 INITIALLY AND NOW THE MOST 233 00:10:35,359 --> 00:10:37,227 RECENT EXPRESSIONS OF INTEREST 234 00:10:37,227 --> 00:10:38,362 INCLUDE EIGHT INSTITUTES. 235 00:10:38,362 --> 00:10:40,464 A GROWING NUMBER OF PARTICIPANTS 236 00:10:40,464 --> 00:10:44,968 AS THE AWARDS HAVE GROWN AND 237 00:10:44,968 --> 00:10:47,137 THIS COMES FROM THE INITIATIVE. 238 00:10:47,137 --> 00:10:50,941 THOSE FAMILIAR WITH RCDC CODING 239 00:10:50,941 --> 00:10:54,011 THE WAY WE PUBLICLY REPORT 240 00:10:54,011 --> 00:10:55,379 THERE'S NOT A SYNTHETIC BIOLOGY 241 00:10:55,379 --> 00:10:56,680 CODE SO IT'S DIFFICULT TO TEASE 242 00:10:56,680 --> 00:10:56,947 OUT. 243 00:10:56,947 --> 00:11:00,350 YOU CAN REACH OUT TO THE 244 00:11:00,350 --> 00:11:02,252 INSTITUTES REPRESENTED HERE TO 245 00:11:02,252 --> 00:11:04,154 GET AN IDEA AT A HIGHER LEVEL 246 00:11:04,154 --> 00:11:05,822 WHAT MAY THEY BE FUNDING BUT 247 00:11:05,822 --> 00:11:09,693 THIS IS FOCUSSED ON THE ACTIVES 248 00:11:09,693 --> 00:11:12,229 OF THE CONSORTIA ITSELF. 249 00:11:12,229 --> 00:11:14,865 HERE'S A KEY WORD SNAPSHOT OF 250 00:11:14,865 --> 00:11:16,133 THE WORK SUPPORTED. 251 00:11:16,133 --> 00:11:18,702 IT'S NO SURPRISED TO MANY IN THE 252 00:11:18,702 --> 00:11:21,838 ROOM WITH THE COURT TERMS AND 253 00:11:21,838 --> 00:11:24,308 GENETIC PROGRAMMING, DIRECTED 254 00:11:24,308 --> 00:11:27,611 EVOLUTION, T CELLS, LIVING CELLS 255 00:11:27,611 --> 00:11:29,313 AND DNA AND THE SUBORDINATE 256 00:11:29,313 --> 00:11:31,048 EMPHASIS WHICH COVER A WIDE 257 00:11:31,048 --> 00:11:33,317 RANGE OF DISEASES AND 258 00:11:33,317 --> 00:11:36,053 APPROACHES. 259 00:11:36,053 --> 00:11:39,256 THEN FINALLY LOOKING AT SOME 260 00:11:39,256 --> 00:11:41,491 RECENT AND FUTURE ACTIVITIES. 261 00:11:41,491 --> 00:11:43,694 I HAD MENTIONED THE NOTICE OF 262 00:11:43,694 --> 00:11:44,628 SPECIAL INTEREST THAT WAS LISTED 263 00:11:44,628 --> 00:11:46,730 ON THE BOTTOM OF THE COMPART. 264 00:11:46,730 --> 00:11:52,269 IT WAS RE-ISSUED CONTINUED TO 265 00:11:52,269 --> 00:11:55,138 STATE THE CONSORTIUM'S INTEREST 266 00:11:55,138 --> 00:11:56,773 AND THERE'S EIGHT INSTITUTES ON 267 00:11:56,773 --> 00:11:56,940 IT. 268 00:11:56,940 --> 00:11:59,976 CALLING OUT TOOLS AND 269 00:11:59,976 --> 00:12:03,113 TECHNOLOGIES TO CONTROL 270 00:12:03,113 --> 00:12:03,814 REPROGRAMMING, APPLYING 271 00:12:03,814 --> 00:12:06,216 SYNTHETIC BIOLOGY TO DEVELOPMENT 272 00:12:06,216 --> 00:12:09,319 OF BIOLOGY AND INCREASING 273 00:12:09,319 --> 00:12:11,555 FUNDAMENTAL UNDERSTANDING AND 274 00:12:11,555 --> 00:12:13,890 CONCEPTS AND GAINING FUNDAMENTAL 275 00:12:13,890 --> 00:12:17,294 KNOWLEDGE THROUGH APPLICATION OF 276 00:12:17,294 --> 00:12:19,696 BIOLOGICAL APPROACHES. 277 00:12:19,696 --> 00:12:24,601 IF YOU HAVE QUESTIONS REACH OUT 278 00:12:24,601 --> 00:12:26,103 TO THE PROGRAM DIRECTORS IN THE 279 00:12:26,103 --> 00:12:28,705 NOTICE AND BRING PROJECTS 280 00:12:28,705 --> 00:12:29,673 RELEVANT TO THE MISSION OF THE 281 00:12:29,673 --> 00:12:30,340 INSTITUTE PARTICIPATING ON THE 282 00:12:30,340 --> 00:12:34,077 INITIATIVES. 283 00:12:34,077 --> 00:12:40,050 RECENTLY THE NIBIB AND NIA HAD A 284 00:12:40,050 --> 00:12:45,088 SYNTHETIC BIOLOGY WORKSHOP TO 285 00:12:45,088 --> 00:12:48,158 PROMOTE THE AGING RESEARCHERS 286 00:12:48,158 --> 00:12:49,726 AND IT'S LIKE SPEED DATING WHERE 287 00:12:49,726 --> 00:12:51,128 THERE WERE QUICK TALKS ON WHAT 288 00:12:51,128 --> 00:12:52,696 THEY'RE DOING RESEARCH ON AND 289 00:12:52,696 --> 00:12:54,297 THEN THEY GOT TOGETHER IN 290 00:12:54,297 --> 00:12:55,732 BREAKOUT SESSIONS. 291 00:12:55,732 --> 00:12:57,934 LATER THIS YEAR OR EARLY NEXT 292 00:12:57,934 --> 00:12:58,869 YEAR THERE'LL BE A REPORT 293 00:12:58,869 --> 00:13:00,070 AVAILABLE ON THE WEBSITE TO 294 00:13:00,070 --> 00:13:02,806 DISCUSS THE OUTCOME AND I THINK 295 00:13:02,806 --> 00:13:05,509 JEMONT IF I RECALL, THERE'S A 296 00:13:05,509 --> 00:13:07,611 VIDEOCAST RECORDING THAT WILL BE 297 00:13:07,611 --> 00:13:09,212 AVAILABLE AS WELL, YEAH. 298 00:13:09,212 --> 00:13:13,016 THANK YOU. 299 00:13:13,016 --> 00:13:16,520 IN THE PLANNING STAGES RIGHT NOW 300 00:13:16,520 --> 00:13:20,357 IS ANTICIPATED FOR FALL OF 2024 301 00:13:20,357 --> 00:13:24,127 AN NHLBI, NIBIB TEAMING UP ON 302 00:13:24,127 --> 00:13:25,095 SYNTHETIC BIOLOGY TO MATCH THE 303 00:13:25,095 --> 00:13:27,264 TOOL BUILDERS TO THE TOOL USERS. 304 00:13:27,264 --> 00:13:30,600 SIMILAR TO THE THEORY OF WHAT 305 00:13:30,600 --> 00:13:33,336 WAS DONE WITH THE NIA TO BRING 306 00:13:33,336 --> 00:13:35,539 THE USERS AND DEVELOPERS 307 00:13:35,539 --> 00:13:37,340 TOGETHER TO DEVELOP THE 308 00:13:37,340 --> 00:13:42,345 PRODUCTS. 309 00:13:42,345 --> 00:13:45,315 SO WITH THAT I'LL END MY 310 00:13:45,315 --> 00:13:47,150 WELCOMING REMARKS AND REALLY 311 00:13:47,150 --> 00:13:48,418 EXCITED WE'RE BEING ABLE TO HOLD 312 00:13:48,418 --> 00:13:49,519 THIS MEETING IN PERSON. 313 00:13:49,519 --> 00:13:51,555 I WANT TO DRAW YOUR ATTENTION TO 314 00:13:51,555 --> 00:13:54,858 THE TENTATIVE PLAN FOR NEXT YEAR 315 00:13:54,858 --> 00:13:57,928 WHICH WILL BE ABOUT THIS TIME IN 316 00:13:57,928 --> 00:13:58,128 2024. 317 00:13:58,128 --> 00:13:58,895 THANK YOU VERY MUCH AGAIN FOR 318 00:13:58,895 --> 00:14:01,064 ATTENDING AND HOPE YOU HAVE A 319 00:14:01,064 --> 00:14:03,366 PRODUCTIVE MEETING TODAY AND 320 00:14:03,366 --> 00:14:03,633 TOMORROW. 321 00:14:03,633 --> 00:14:05,335 PLEASE ENJOY DISCUSSING WITH 322 00:14:05,335 --> 00:14:07,504 YOUR COLLEAGUES, MEET SOME NEW 323 00:14:07,504 --> 00:14:08,905 PEOPLE WHO MAYBE YOU HAVEN'T MET 324 00:14:08,905 --> 00:14:09,206 YET. 325 00:14:09,206 --> 00:14:11,975 IF YOU HAVE QUESTIONS ABOUT THE 326 00:14:11,975 --> 00:14:14,277 WORKSHOP, CONTACT JEMONT OR 327 00:14:14,277 --> 00:14:16,947 NICOLE OR OUR WORKSHOP 328 00:14:16,947 --> 00:14:19,249 CONTRACTOR OF STRATEGIC RESULTS 329 00:14:19,249 --> 00:14:22,752 AND THANK YOU TO THE NIH BIOLOGY 330 00:14:22,752 --> 00:14:24,454 CONSORTIA MEMBERS AND OUR 331 00:14:24,454 --> 00:14:28,191 CONTRACTORS TO DEVELOP THE 332 00:14:28,191 --> 00:14:31,261 WORKSHOP AND NIH FOUNDATION FOR 333 00:14:31,261 --> 00:14:32,362 THE ADVANCED EDUCATION IN THE 334 00:14:32,362 --> 00:14:34,164 SCIENCES FOR THE COFFEE BREAKS. 335 00:14:34,164 --> 00:14:35,665 THANK YOU, EVERYONE AND WELCOME 336 00:14:35,665 --> 00:14:46,176 AND HAVE A FANTASTIC MEETING. 337 00:14:54,160 --> 00:14:54,561 THANK YOU. 338 00:14:54,561 --> 00:14:58,031 SO TODAY I'M GOING TO BE 339 00:14:58,031 --> 00:14:59,866 DISCUSSING MY RESEARCH ON 340 00:14:59,866 --> 00:15:02,535 ESSENTIALLY A VERY NEW TYPE OF 341 00:15:02,535 --> 00:15:04,904 TECHNOLOGY AND AT THIS POINT 342 00:15:04,904 --> 00:15:06,272 CURRENTLY A WORK IN PROGRESS BUT 343 00:15:06,272 --> 00:15:11,644 SOMETHING THAT I'M VERY EXCITED 344 00:15:11,644 --> 00:15:17,116 ABOUT I'M GOING TO TALK ABOUT 345 00:15:17,116 --> 00:15:18,852 THREE DIFFERENT GENE THERAPY 346 00:15:18,852 --> 00:15:22,856 VEHICLES I'M IN THE STAGES OF 347 00:15:22,856 --> 00:15:24,691 DEVELOPING ON REALLY I'VE 348 00:15:24,691 --> 00:15:27,093 ENGINEERED THESE AND NOW IN THE 349 00:15:27,093 --> 00:15:29,195 PROCESS OF TESTING THEM. 350 00:15:29,195 --> 00:15:30,864 SO I'M GOING TO BE MAINLY 351 00:15:30,864 --> 00:15:32,031 FOCUSSING TODAY ON THE 352 00:15:32,031 --> 00:15:35,034 ENGINEERING PART, THE DESIGN AND 353 00:15:35,034 --> 00:15:36,836 BUILD PART SINCE THAT'S WHERE I 354 00:15:36,836 --> 00:15:38,972 HAVE THE MOST INTERESTING DATA 355 00:15:38,972 --> 00:15:41,841 SO FAR BUT REST ASSURED THAT I 356 00:15:41,841 --> 00:15:49,549 AM WELL ON MY WAY TO DEVELOPING 357 00:15:49,549 --> 00:15:51,351 CELL BASED IN VITRO ASSAYS AND 358 00:15:51,351 --> 00:15:54,053 HOPE TO SCALE UP TO IN VIVO 359 00:15:54,053 --> 00:15:59,125 ASSAYS IN THE COMING YEARS. 360 00:15:59,125 --> 00:16:03,229 SO MOLECULAR GLUE WAS TITLED AND 361 00:16:03,229 --> 00:16:06,332 HOW DOES IT DESIGN THE NOVEL 362 00:16:06,332 --> 00:16:07,200 GENE THERAPY SYSTEMS? 363 00:16:07,200 --> 00:16:11,905 WHAT I'M USING IS THE SPAY 364 00:16:11,905 --> 00:16:14,340 TAG-SPY CATCHER SYSTEM 365 00:16:14,340 --> 00:16:17,310 ENGINEERED PEPTIDES WHICH REACT 366 00:16:17,310 --> 00:16:18,945 IN A HIGHLY SPECIFIC AND 367 00:16:18,945 --> 00:16:23,116 EFFICIENT FASHION TO FORM A 368 00:16:23,116 --> 00:16:25,652 COVALENT PEPTIDE WITH EACH OTHER 369 00:16:25,652 --> 00:16:27,921 ALLOWING FOR THE LINKAGE OF 370 00:16:27,921 --> 00:16:30,356 PROTEINS AND ALLOWS FOR 371 00:16:30,356 --> 00:16:32,859 ESSENTIALLY ANYTHING TO BE STUCK 372 00:16:32,859 --> 00:16:35,395 TOGETHER IN THE FASHION THAT 373 00:16:35,395 --> 00:16:37,130 ESSENTIALLY YOU CAN MIX THEM AND 374 00:16:37,130 --> 00:16:38,331 THEY'LL JUST LINK WHICH IS 375 00:16:38,331 --> 00:16:41,100 AMAZING. 376 00:16:41,100 --> 00:16:43,569 TO START I'M GOING TO TALK ABOUT 377 00:16:43,569 --> 00:16:48,841 THE FIRST GENE DELIVERY SYSTEM 378 00:16:48,841 --> 00:16:52,946 THAT I AM NOT CHRONOLOGICALLY 379 00:16:52,946 --> 00:16:56,716 FIRST BUT THE FIRST IS CALLED 380 00:16:56,716 --> 00:16:58,318 VAULT AAV. 381 00:16:58,318 --> 00:17:01,387 AAVs ARE A LEADING GENE THERAPY 382 00:17:01,387 --> 00:17:01,821 DELIVERY SYSTEM. 383 00:17:01,821 --> 00:17:04,057 I'M SURE MANY ARE AWARE. 384 00:17:04,057 --> 00:17:05,925 HOWEVER, THERE IS A MAJOR 385 00:17:05,925 --> 00:17:09,095 PROBLEM WITH AAVs IN THAT 30% TO 386 00:17:09,095 --> 00:17:11,497 60% OF PATIENTS ALREADY HAVE 387 00:17:11,497 --> 00:17:13,967 PRE-EXISTING ANTIBODIES WHICH 388 00:17:13,967 --> 00:17:16,235 MAKE THEM OFTEN TIMES INELIGIBLE 389 00:17:16,235 --> 00:17:19,672 FOR TREATMENT OR REQUIRE VERY 390 00:17:19,672 --> 00:17:20,640 COMPLICATED INTERVENTIONS TO 391 00:17:20,640 --> 00:17:22,175 MITIGATE THIS ISSUE SUCH AS 392 00:17:22,175 --> 00:17:23,076 REMOVING PARTS OF THEIR PLASMA 393 00:17:23,076 --> 00:17:31,951 AND SO ON AND SO FORTH. 394 00:17:31,951 --> 00:17:33,786 AND THEY HAVE POTENTIAL AND 395 00:17:33,786 --> 00:17:35,855 CLINICALLY APPROVED FOR FIVE FDA 396 00:17:35,855 --> 00:17:36,823 APPROVED THERAPIES NOW IF I 397 00:17:36,823 --> 00:17:37,223 RECALL CORRECTLY. 398 00:17:37,223 --> 00:17:38,358 AVE AVE 399 00:17:50,737 --> 00:17:56,776 AAVs ARE AWESOME BUT THESE ARE 400 00:17:56,776 --> 00:17:59,579 EXPRESSED IN MOST CELLS 401 00:17:59,579 --> 00:18:00,847 INCLUDING HUMAN CELLS AND 402 00:18:00,847 --> 00:18:06,853 THEY'LL PACK DURING A PEPTIDE 403 00:18:06,853 --> 00:18:17,363 CALLED INT AND PHAGOCYTES AND 404 00:18:18,664 --> 00:18:22,301 AAVs HAVE A BUILT IN MECHANISM 405 00:18:22,301 --> 00:18:24,837 FOR ESCAPING ENDOSOME SINCE 406 00:18:24,837 --> 00:18:28,741 THEY'RE A VIRUS USING THEIR 407 00:18:28,741 --> 00:18:29,042 LIPASE. 408 00:18:29,042 --> 00:18:30,710 THIS IS WHAT I PLAN TO DO 409 00:18:30,710 --> 00:18:35,415 HOPEFULLY IN THE NEXT FEW WEEKS, 410 00:18:35,415 --> 00:18:37,116 ESSENTIALLY A VAULT WHICH HAS 411 00:18:37,116 --> 00:18:44,457 PACKAGED AN AAV WILL BE PACKAGED 412 00:18:44,457 --> 00:18:46,793 AND ESCAPE AND CIRCUMVENT THE 413 00:18:46,793 --> 00:18:48,327 PRESENCE OF ANY ANTIBODIES WHICH 414 00:18:48,327 --> 00:18:51,164 MAY BE PRESENT IN THE SOLUTION. 415 00:18:51,164 --> 00:18:53,332 EEL TALK MORE ABOUT THE ASSAY 416 00:18:53,332 --> 00:19:03,876 I'M WORKING ON FOR THAT DID DEF 417 00:19:11,084 --> 00:19:13,286 YOU SEE SOME PACKAGED HERE AND 418 00:19:13,286 --> 00:19:14,654 HERE, ETCETERA AND THERE'S A 419 00:19:14,654 --> 00:19:17,990 CONTROL WHERE THERE'S NO 420 00:19:17,990 --> 00:19:19,692 PACKAGING BECAUSE I DIDN'T HAVE 421 00:19:19,692 --> 00:19:26,232 THE I.N.T. PEPTIDE AND WHERE THE 422 00:19:26,232 --> 00:19:28,568 MOLECULAR GLUE COMES IN IT HAS A 423 00:19:28,568 --> 00:19:30,903 SPY TAG ON THE PROTEIN AND THE 424 00:19:30,903 --> 00:19:33,239 SPY CATCHER IS FUSED TO THE 425 00:19:33,239 --> 00:19:38,377 I.N.T. PEPTIDE AND THIS PRODUCES 426 00:19:38,377 --> 00:19:41,881 AAV WITH I.N.T. AND MIX IT WITH 427 00:19:41,881 --> 00:19:47,286 THE VAULT AND OVERNIGHT YOU GET 428 00:19:47,286 --> 00:19:49,589 THE PACKAGING WHICH IS GREAT. 429 00:19:49,589 --> 00:19:53,359 YOU SEE NICELY PACKAGED AAVs 430 00:19:53,359 --> 00:19:54,894 INSIDE THE JAR LIKE VAULTS AND 431 00:19:54,894 --> 00:19:56,329 SEE HOW THIS CAN PROTECT THEM 432 00:19:56,329 --> 00:19:59,031 AND AS I MENTIONED I'M NOW 433 00:19:59,031 --> 00:20:02,368 DEVELOPING THIS ASSAY WHERE I'M 434 00:20:02,368 --> 00:20:05,538 USING ANTI-AAV ANTIBODIES AND 435 00:20:05,538 --> 00:20:07,406 I'M INTENDING TO HOPEFULLY LIKE 436 00:20:07,406 --> 00:20:09,842 I SAID IN THE NEXT FEW WEEKS GET 437 00:20:09,842 --> 00:20:11,577 THE DATA IT SHOW THIS PROCESS 438 00:20:11,577 --> 00:20:13,613 WORKING AND HAVING EFFICACY. 439 00:20:13,613 --> 00:20:14,013 ALL RIGHT. 440 00:20:14,013 --> 00:20:16,015 SO I'M GOING TO MOVE ON TO THE 441 00:20:16,015 --> 00:20:20,553 NEXT SYSTEM I'M DEVELOPING NOW. 442 00:20:20,553 --> 00:20:24,891 IT'S CALLED ADD AAV AND THIS IS 443 00:20:24,891 --> 00:20:26,692 CHRONOLOGICALLY THE FIRST I 444 00:20:26,692 --> 00:20:29,262 WORKED ON AND THIS IS ANOTHER 445 00:20:29,262 --> 00:20:30,963 GREAT VIRAL VECTOR IS 446 00:20:30,963 --> 00:20:31,531 ADENOVIRUS. 447 00:20:31,531 --> 00:20:33,232 I WON'T GO IN THE BENEFITS AND 448 00:20:33,232 --> 00:20:34,333 DRAWBACKS RIGHT NOW BUT YOU CAN 449 00:20:34,333 --> 00:20:36,903 TALK TO ME LATER IF YOU'D LIKE. 450 00:20:36,903 --> 00:20:39,405 THEY BOTH HAVE POTENTIAL FOR 451 00:20:39,405 --> 00:20:41,007 FUTURE CRISPR KAS APPLICATIONS 452 00:20:41,007 --> 00:20:44,076 WHICH IS EXCITING BUT WHAT IF WE 453 00:20:44,076 --> 00:20:46,045 CAN COMBINE THESE VEHICLES? 454 00:20:46,045 --> 00:20:50,349 LINKING THEM TO THE ADENO 455 00:20:50,349 --> 00:20:54,253 SURFACE MITIGATING DRAWBACKS AND 456 00:20:54,253 --> 00:20:58,357 ENABLING COMPLEX MULTIGENIC 457 00:20:58,357 --> 00:20:59,792 DELIVERY TO THE SAME CELL IN A 458 00:20:59,792 --> 00:21:04,597 HIGHLY EFFICIENT FASHION. 459 00:21:04,597 --> 00:21:07,600 AND I HAVE MADE GENETIC CAPSID 460 00:21:07,600 --> 00:21:08,901 MODIFICATIONS IN COLLABORATION 461 00:21:08,901 --> 00:21:13,439 WITH OTHER FOLKS IN MY LAB AND 462 00:21:13,439 --> 00:21:14,807 COLLABORATORS AND IN EXTERNAL 463 00:21:14,807 --> 00:21:18,444 LAB AT BAYLOR UNIVERSITY. 464 00:21:18,444 --> 00:21:21,847 WE WERE ABLE TO ASSEMBLE 465 00:21:21,847 --> 00:21:25,017 ESSENTIALLY ADENOVIRUS WITH 466 00:21:25,017 --> 00:21:27,787 HEXON SPY TAG THE 720 COPY IN 467 00:21:27,787 --> 00:21:32,692 THE CAPSID AND THERE'S A SPY TAG 468 00:21:32,692 --> 00:21:36,896 AT EACH OF THOSE THREE SPY TAGS 469 00:21:36,896 --> 00:21:44,170 PER TRIMER AND WE ALSO HAVE BP2 470 00:21:44,170 --> 00:21:46,339 SPY TAG ON AAV AND IT ONLY 471 00:21:46,339 --> 00:21:51,377 OCCURS AT A 1 IN EVERY 10 472 00:21:51,377 --> 00:21:53,980 PROTEINS IN THE CAPSID AND END 473 00:21:53,980 --> 00:21:56,282 UP WITH FIVE BP2 SPY TAGS. 474 00:21:56,282 --> 00:21:59,085 THIS IS ESSENTIALLY HOW WE'RE 475 00:21:59,085 --> 00:22:02,755 STARTING OFF AND WE NEED TO 476 00:22:02,755 --> 00:22:03,756 COMBINE THEM. 477 00:22:03,756 --> 00:22:05,491 SO I'M NOT GOING IN THE DETAILS 478 00:22:05,491 --> 00:22:06,993 OF THIS FOR SAKE OF TIME BECAUSE 479 00:22:06,993 --> 00:22:10,429 IT'S A LIGHTNING TALK BUT I 480 00:22:10,429 --> 00:22:12,965 DEVISED AN ASSEMBLY AND FUR 481 00:22:12,965 --> 00:22:14,767 FICTION TECHNIQUE WHICH YIELDS 482 00:22:14,767 --> 00:22:15,368 THE AAVs. 483 00:22:15,368 --> 00:22:18,070 I'LL SHOW YOU SOME OF THE 484 00:22:18,070 --> 00:22:20,640 ASSEMBLY TESTS WITHOUT 485 00:22:20,640 --> 00:22:24,443 PURIFICATION FIRST TO SHOW NICE 486 00:22:24,443 --> 00:22:26,679 IMAGES OF AAVs AND THERE'S NO 487 00:22:26,679 --> 00:22:28,514 CONTROL ON THE ADENOVIRUS AND 488 00:22:28,514 --> 00:22:32,318 WHAT YOU CAN SEE IS THE ADD AAVs 489 00:22:32,318 --> 00:22:33,886 ASSEMBLE NICELY IN MANY CASES. 490 00:22:33,886 --> 00:22:38,424 I ESPECIALLY LIKE THIS ONE SO ON 491 00:22:38,424 --> 00:22:40,826 AND SO FORTH AND YOU CAN GET A 492 00:22:40,826 --> 00:22:43,429 NUMBER OF AAVs PER ADENOVIRUS 493 00:22:43,429 --> 00:22:46,332 MAYBE AROUND 10 IF IT'S A GOOD 494 00:22:46,332 --> 00:22:46,565 BATCH. 495 00:22:46,565 --> 00:22:51,203 SO THEN THERE'S THE PURIFICATION 496 00:22:51,203 --> 00:22:54,006 AND THESE ARE IMAGES AND YOU CAN 497 00:22:54,006 --> 00:22:56,609 SEE BEFORE AND AFTER THE 498 00:22:56,609 --> 00:22:59,445 PURIFICATION IT'S ABLE TO 499 00:22:59,445 --> 00:23:00,913 ELIMINATE MOST THE FREE AAVs IN 500 00:23:00,913 --> 00:23:03,149 THE AGGREGATES AND NOW I'M 501 00:23:03,149 --> 00:23:06,452 DEVELOPING ASSAYS TO SHOW 502 00:23:06,452 --> 00:23:08,154 MULTI-GENIC CO-DUCTION OF ADD 503 00:23:08,154 --> 00:23:09,889 AAVs AND ALSO WORKING WITH OTHER 504 00:23:09,889 --> 00:23:11,691 MEMBERS OF MY LAB TO DEVELOP A 505 00:23:11,691 --> 00:23:14,860 MORE STREAMLINED ASSEMBLY 506 00:23:14,860 --> 00:23:17,663 PROCESS THAT MAYBE WILL HAVE 507 00:23:17,663 --> 00:23:22,335 HIGHER YIELDS AND ALSO ENFORCE 508 00:23:22,335 --> 00:23:24,537 TO A DIFFERENT SET OF TYPES AND 509 00:23:24,537 --> 00:23:25,871 ADENOVIRUS AND AAV TO BROADEN 510 00:23:25,871 --> 00:23:29,208 THE OPTIONS FOR WHAT TYPES OF 511 00:23:29,208 --> 00:23:30,609 CELLS ARE MOST SUFFICIENTLY 512 00:23:30,609 --> 00:23:31,243 TRANSDUCED. 513 00:23:31,243 --> 00:23:33,813 FINALLY I'M GOING TO TALK 514 00:23:33,813 --> 00:23:36,582 BRIEFLY ABOUT ADD MS2 OR ADD 515 00:23:36,582 --> 00:23:40,653 PHAGE THE FIRST AND PROBABLY THE 516 00:23:40,653 --> 00:23:42,922 LEAST FULLY DEVELOPED TECHNOLOGY 517 00:23:42,922 --> 00:23:47,760 BUT STILL VERY COOL. 518 00:23:47,760 --> 00:23:51,797 SO WHAT AD MS2 IS A SMALL 519 00:23:51,797 --> 00:23:54,033 BACTERIA PHAGE NOT THE TYPES 520 00:23:54,033 --> 00:23:56,235 WHERE YOU SEE THE TAIL FIBERS 521 00:23:56,235 --> 00:23:58,337 AND SPUTNIK LANDER LOOKING 522 00:23:58,337 --> 00:24:04,844 THINGS BUT A BACTERIAL PHAGE 523 00:24:04,844 --> 00:24:07,046 WHICH IS CARRIES RNA. 524 00:24:07,046 --> 00:24:09,882 IT'S LIKE AN RNA VARIANT OF AD 525 00:24:09,882 --> 00:24:12,818 AAV AND HAS APPLICATIONS. 526 00:24:12,818 --> 00:24:15,254 ADENOVIRUS IS GREAT AS AN 527 00:24:15,254 --> 00:24:21,394 INTRANASAL DELIVERY AND WE HAD A 528 00:24:21,394 --> 00:24:23,863 VACCINE APPROVED BY THE HEALTH 529 00:24:23,863 --> 00:24:26,365 OFFICIALS IN INDIA AND PASSED 530 00:24:26,365 --> 00:24:27,767 PHASE III CLINICAL TRIALS AND 531 00:24:27,767 --> 00:24:30,803 NOW ON THE MARKET IN INDIA AND 532 00:24:30,803 --> 00:24:34,373 SO WHAT I'M DOING IS I AM TRYING 533 00:24:34,373 --> 00:24:38,344 TO DEVELOP A WAY OF AVERAGE A 534 00:24:38,344 --> 00:24:41,313 MORE EFFICACIOUS RNA ADENOVIRUS 535 00:24:41,313 --> 00:24:43,916 VEHICLES WHERE THE ADENOVIRUS 536 00:24:43,916 --> 00:24:46,419 SERVES AS A DELIVERY VEHICLE TO 537 00:24:46,419 --> 00:24:54,360 TRANSDUCE THE MUCOSA ACTING AS 538 00:24:54,360 --> 00:24:58,998 AN IMMUNITY BLOCK AT THE SITE OF 539 00:24:58,998 --> 00:25:00,933 ENTRY AND AT THE SAME TIME 540 00:25:00,933 --> 00:25:02,334 TRYING TO MAKE IT MORE EFFICIENT 541 00:25:02,334 --> 00:25:03,702 THAN WHAT WE CURRENTLY HAVE 542 00:25:03,702 --> 00:25:05,371 DEVELOPED IN THE LAB BY PROTECT 543 00:25:05,371 --> 00:25:11,977 THE RNA MOLECULE WITH THIS 544 00:25:11,977 --> 00:25:12,945 BACTERIAL PHAGE CELL. 545 00:25:12,945 --> 00:25:16,015 I'M USING A SIMILAR SYSTEM OF 546 00:25:16,015 --> 00:25:16,916 ASSEMBLY AND PURIFICATION. 547 00:25:16,916 --> 00:25:18,651 YOU CAN SEE HERE WE HAVE THE 548 00:25:18,651 --> 00:25:20,085 SAME PROCESS. 549 00:25:20,085 --> 00:25:22,588 WE HAVE THE NICE AD MS2s IN THE 550 00:25:22,588 --> 00:25:24,256 ROW OVER THERE AND THE CONTROL 551 00:25:24,256 --> 00:25:26,358 AND THEN WE HAVE OUR 552 00:25:26,358 --> 00:25:29,562 PURIFICATION PROCESS WHICH IS 553 00:25:29,562 --> 00:25:30,196 VERY SIMILAR. 554 00:25:30,196 --> 00:25:33,432 SO HOWEVER, THIS PURIFICATION 555 00:25:33,432 --> 00:25:34,500 PROCESS HAS BEEN A LITTLE BIT 556 00:25:34,500 --> 00:25:36,469 CUMBERSOME IN SOME CASES SO TO 557 00:25:36,469 --> 00:25:38,337 STREAMLINE IT WE'RE ACTUALLY 558 00:25:38,337 --> 00:25:41,040 WORKING WITH COLLABORATORS TO 559 00:25:41,040 --> 00:25:43,108 ADD SPY TAG ON TO THE MATURATION 560 00:25:43,108 --> 00:25:44,643 PROTEIN OF THE PHAGE WHICH IS A 561 00:25:44,643 --> 00:25:47,146 SINGLE COPY PROTEIN IN THE 562 00:25:47,146 --> 00:25:47,546 CAPSID. 563 00:25:47,546 --> 00:25:50,883 THIS WILL ENABLE MUCH SIMPLER 564 00:25:50,883 --> 00:25:52,017 ASSEMBLY PROCESS TO A CLICK AND 565 00:25:52,017 --> 00:25:57,690 GO AND FOR PROOF OF PRINCIPLE 566 00:25:57,690 --> 00:26:07,967 WE'RE WORK WITH 5CB5 TO BIND A 567 00:26:07,967 --> 00:26:09,635 FLUOROPHOR AS PROOF OF CONCEPT 568 00:26:09,635 --> 00:26:13,439 AND ACT AS AN ENHANCED VACCINE 569 00:26:13,439 --> 00:26:15,841 RELEVANT TO WHAT OUR INTRANASAL 570 00:26:15,841 --> 00:26:17,843 VACCINES ARE CAPABLE OF DOING 571 00:26:17,843 --> 00:26:21,680 AND IT WILL BE YET ANOTHER 572 00:26:21,680 --> 00:26:22,848 APPLICATION OF MOLECULAR GLUE 573 00:26:22,848 --> 00:26:24,583 FOR THE PURPOSES OF GENE 574 00:26:24,583 --> 00:26:25,017 DELIVERY. 575 00:26:25,017 --> 00:26:26,252 WITH THAT I WILL CONCLUDE AND I 576 00:26:26,252 --> 00:26:36,595 WILL TAKE QUESTIONS. 577 00:26:47,106 --> 00:26:50,109 >> THANK YOU FOR THE TALK. 578 00:26:50,109 --> 00:26:52,811 I'M INTERESTED IN THE DELIVERY 579 00:26:52,811 --> 00:26:53,979 SYSTEM AND THE DES ASSEMBLY. 580 00:26:53,979 --> 00:26:58,217 HOW DO YOU MAKE IT SO IT DOESN'T 581 00:26:58,217 --> 00:26:59,685 DISASSEMBLE BEFORE IT GETS TO 582 00:26:59,685 --> 00:26:59,985 ITS TARGET? 583 00:26:59,985 --> 00:27:04,390 >> ESSENTIALLY THE VAULTS ARE 584 00:27:04,390 --> 00:27:06,892 PRETTY STABLE UNDER 585 00:27:06,892 --> 00:27:08,794 PHYSIOLOGICAL PH CONDITION BUT 586 00:27:08,794 --> 00:27:11,897 THE DISASSEMBLY HAPPENS WHEN THE 587 00:27:11,897 --> 00:27:15,968 PH GETS LOWER. 588 00:27:15,968 --> 00:27:17,469 AROUND 5 OR 4 THE VAULTS START 589 00:27:17,469 --> 00:27:19,939 TO COME APARD AND THIS IS 590 00:27:19,939 --> 00:27:21,907 ACTUALLY SOMETHING THAT HAS BEEN 591 00:27:21,907 --> 00:27:23,642 WELL DOCUMENTED IN THE 592 00:27:23,642 --> 00:27:25,678 LITERATURE AND WHAT CAN HAPPEN 593 00:27:25,678 --> 00:27:28,480 THEN IS YOU CAN IMAGINE ONCE THE 594 00:27:28,480 --> 00:27:32,284 ENDOSOME BEGINS TO ACIDIFY WILL 595 00:27:32,284 --> 00:27:35,654 RELEASE THE AAV THROUGH VAULT 596 00:27:35,654 --> 00:27:38,324 DISASSEMBLY AND THE AAV WILL BE 597 00:27:38,324 --> 00:27:42,928 ABLE TO EMPLOY IT'S OWN ACID 598 00:27:42,928 --> 00:27:46,332 TRIGGERED PHOSPHOLIPASE TO GO 599 00:27:46,332 --> 00:27:48,934 OUT TO THE NORMAL PATHWAY FOR 600 00:27:48,934 --> 00:27:49,535 GENE TRANSDUCTION. 601 00:27:49,535 --> 00:27:49,868 >> VERY COOL. 602 00:27:49,868 --> 00:27:50,936 THANK YOU. 603 00:27:50,936 --> 00:27:54,773 >> WELCOME. 604 00:27:54,773 --> 00:27:58,310 ANY OTHER QUESTIONS? 605 00:27:58,310 --> 00:27:58,944 ALL RIGHT. 606 00:27:58,944 --> 00:28:09,455 THANK YOU VERY MUCH, EVERYONE. 607 00:28:10,422 --> 00:28:13,025 >> WE'LL HAVE OUR SECOND 608 00:28:13,025 --> 00:28:15,961 LIGHTNING TALK OF THE POSSESSION 609 00:28:15,961 --> 00:28:19,098 BY PARISA YOUSEFPOUR TEMPORAL 610 00:28:19,098 --> 00:28:21,700 CONTROLLED GENE EXPRESSION AND 611 00:28:21,700 --> 00:28:24,503 SMALL MOLECULE SELF-REPLICATING 612 00:28:24,503 --> 00:28:35,014 RNAs FOR CANCER IMMUNOTHERAPY. 613 00:28:43,956 --> 00:28:44,790 >> HI. 614 00:28:44,790 --> 00:28:51,530 THIS IS ACTUALLY MY FIRST IN 615 00:28:51,530 --> 00:29:00,939 PERSON TALK TO A SYNTHETIC 616 00:29:00,939 --> 00:29:04,276 BIOLOGY AUDIENCE AND THIS IS 617 00:29:04,276 --> 00:29:05,944 LOOKING AT SELF-REPLICATING RNAs 618 00:29:05,944 --> 00:29:09,882 FOR TEMPORAL CONTROL OF GENE 619 00:29:09,882 --> 00:29:10,182 EXPRESSION. 620 00:29:10,182 --> 00:29:14,319 SO CANCER IMMUNOTHERAPY HAS 621 00:29:14,319 --> 00:29:15,187 REVOLUTIONIZED MANY FORMS OF 622 00:29:15,187 --> 00:29:21,093 CANCERS AND A HALLMARK OF CANCER 623 00:29:21,093 --> 00:29:22,961 IN IMMUNOTHERAPY IS THE 624 00:29:22,961 --> 00:29:24,697 INDUCTION OF LONG LASTING 625 00:29:24,697 --> 00:29:24,963 RESPONSES. 626 00:29:24,963 --> 00:29:28,567 BUT THE LIMITATION IS THAT THESE 627 00:29:28,567 --> 00:29:29,868 DURABLE RESPONSES ARE ONLY 628 00:29:29,868 --> 00:29:32,638 OBSERVED IN A SMALL TRACTION OF 629 00:29:32,638 --> 00:29:32,905 PATIENTS. 630 00:29:32,905 --> 00:29:36,075 AND ALSO THESE IMMUNOTHERAPIES 631 00:29:36,075 --> 00:29:38,377 CAN BE ASSOCIATED WITH ADVERSE 632 00:29:38,377 --> 00:29:39,978 SIDE EFFECTS AND AUTO IMMUNE 633 00:29:39,978 --> 00:29:40,546 REACTIONS. 634 00:29:40,546 --> 00:29:46,385 SO THE GOAL OF OUR PROJECT IS TO 635 00:29:46,385 --> 00:29:48,053 DEVELOP NEXT GENERATION RNA 636 00:29:48,053 --> 00:29:52,758 THERAPEUTICS TO ENHANCE THE 637 00:29:52,758 --> 00:29:54,359 EFFICACY AND SAFETY PROFILES OF 638 00:29:54,359 --> 00:29:59,498 CANCER IMMUNOTHERAPIES. 639 00:29:59,498 --> 00:30:04,603 AS I MENTIONED, THE RNA PLATFORM 640 00:30:04,603 --> 00:30:07,606 WE WORK WITH IS SELF-REPLICATING 641 00:30:07,606 --> 00:30:12,144 RNA AND WHAT OUR LAB USE DERIVED 642 00:30:12,144 --> 00:30:15,547 FROM THE ALPHA VIRUS GENOME AND 643 00:30:15,547 --> 00:30:16,615 BINDS STRUCTURAL AND 644 00:30:16,615 --> 00:30:17,950 NON-STRUCTURAL PROTEINS AND 645 00:30:17,950 --> 00:30:21,487 THESE INCLUDE PROTEINS LIKE THE 646 00:30:21,487 --> 00:30:24,323 TRIMER AND CAPSID PROTEINS THAT 647 00:30:24,323 --> 00:30:26,191 FORM THE VIRAL ENVELOPE. 648 00:30:26,191 --> 00:30:36,735 IC MAKING THE REPLICONS AND THE 649 00:30:44,510 --> 00:30:49,214 PROTEINS ARE TRANSLATED AN THIS 650 00:30:49,214 --> 00:30:53,018 COPIES THE ORIGINAL STRAND OF 651 00:30:53,018 --> 00:30:57,656 REPLICON AND GENOME AND THE SUB 652 00:30:57,656 --> 00:31:00,359 GENOMIC TRANSCRIPT RESULTS IN 653 00:31:00,359 --> 00:31:03,395 FOR EXAMPLE CYTOKINES FOR TRANS 654 00:31:03,395 --> 00:31:03,762 IMMUNOTHERAPY. 655 00:31:03,762 --> 00:31:07,900 BECAUSE OF THE SELF-AMPLIFYING 656 00:31:07,900 --> 00:31:09,601 NATURE IT CAN TRANSFUSE IN THE 657 00:31:09,601 --> 00:31:12,204 CELLS FOR A LONG TIME AND ALLOWS 658 00:31:12,204 --> 00:31:13,572 FOR SUSTAINED GENE EXPRESSION 659 00:31:13,572 --> 00:31:15,774 AND WHEN WE USE A REPORTED CARGO 660 00:31:15,774 --> 00:31:18,043 WE WERE ABLE TO DETECT GENE 661 00:31:18,043 --> 00:31:19,812 EXPRESSION AS INDICATED BY THE 662 00:31:19,812 --> 00:31:22,548 SIGNAL FOR OVER MONTHS AND THIS 663 00:31:22,548 --> 00:31:24,650 IS SIGNIFICANTLY LONGER THAN 664 00:31:24,650 --> 00:31:30,389 WHAT CAN BE ACHIEVED WITH 665 00:31:30,389 --> 00:31:32,891 CONVENTIONAL mRNA WHERE GENE 666 00:31:32,891 --> 00:31:33,458 EXPRESSION ONLY LASTS A FEW 667 00:31:33,458 --> 00:31:37,262 DAYS. 668 00:31:37,262 --> 00:31:38,530 IN A PREVIOUS REPORT WE 669 00:31:38,530 --> 00:31:46,004 CONSTRUCTED REPLICONS AND THESE 670 00:31:46,004 --> 00:31:49,842 WERE ENCAPSULATED IN LIPID NANO 671 00:31:49,842 --> 00:31:51,176 PARTICLES. 672 00:31:51,176 --> 00:31:54,813 AND WE OBSERVED THIS REPLICON 673 00:31:54,813 --> 00:32:00,052 FORMULATION WHEN THEY WERE 674 00:32:00,052 --> 00:32:03,422 INJECTED INTO TUMORALLY AND 675 00:32:03,422 --> 00:32:05,557 LOCALLY AND HAD SYSTEMIC 676 00:32:05,557 --> 00:32:06,959 IMMUNOTHERAPY AND WERE ABLE TO 677 00:32:06,959 --> 00:32:11,697 RESULT IN TUMOR REGRESSION IN 678 00:32:11,697 --> 00:32:15,200 INJECTED AND UNINJECTED TUMORS. 679 00:32:15,200 --> 00:32:18,437 THIS LED TO SURVIVAL 50% OF THE 680 00:32:18,437 --> 00:32:24,977 ANIMALS. 681 00:32:24,977 --> 00:32:30,949 IMPORTANTLY IN THIS WORK, WE 682 00:32:30,949 --> 00:32:33,652 INTENTIONALLY USED THE CYTOTOXIC 683 00:32:33,652 --> 00:32:36,655 LIPID NANO PARTICLE TO INDUCE 684 00:32:36,655 --> 00:32:38,023 THE IMMUNOGENIC CELL DEATHS IN 685 00:32:38,023 --> 00:32:40,792 THE INFECTED TUMOR CELLS AND 686 00:32:40,792 --> 00:32:44,229 THESE CELL DEATHS OR ICD IS A 687 00:32:44,229 --> 00:32:45,030 KEY CONTRIBUTOR TO THE STRATEGY 688 00:32:45,030 --> 00:32:49,701 BECAUSE IT RELEASES THE TUMOR 689 00:32:49,701 --> 00:32:52,771 ANTIGENS AND GENERATES AN IN 690 00:32:52,771 --> 00:32:54,973 SITU VACCINATION EFFECT. 691 00:32:54,973 --> 00:32:57,042 WE HYPOTHESIZED WE COULD ENHANCE 692 00:32:57,042 --> 00:33:01,446 THE CURATIVE EFFICACY OF THIS 693 00:33:01,446 --> 00:33:02,314 STRATEGY BY DELAYING THE 694 00:33:02,314 --> 00:33:04,583 INDUCTION OF THE IMMUNOGENIC 695 00:33:04,583 --> 00:33:11,223 CELL DEATHS TO KEEP THE INFECTED 696 00:33:11,223 --> 00:33:13,825 CELLS AND IN FLAME THE TUMOR AND 697 00:33:13,825 --> 00:33:15,027 RECRUIT THE IMMUNE CELLS AND 698 00:33:15,027 --> 00:33:17,663 THEN TRIGGER THE CELL DEATHS TO 699 00:33:17,663 --> 00:33:25,737 RELEASE THE TUMOR ANTIGENS. 700 00:33:25,737 --> 00:33:33,745 SO, TO DO THIS INSTEAD OF USING 701 00:33:33,745 --> 00:33:35,948 CYTOTOXIC LIPID PARTICLES WE 702 00:33:35,948 --> 00:33:44,289 ENCODED FOR IL12 AND CYTOTOXIC 703 00:33:44,289 --> 00:33:45,123 GASES AND TO DELAY THE 704 00:33:45,123 --> 00:33:48,727 EXPRESSION OF THE GAS WE 705 00:33:48,727 --> 00:33:49,361 INCORPORATED SYNTHETIC BIOLOGY 706 00:33:49,361 --> 00:33:52,998 GENE CIRCUITS IN OUR REPLICATE 707 00:33:52,998 --> 00:33:56,368 PLATFORM TO THE EXPRESSION CAN 708 00:33:56,368 --> 00:33:58,103 BE TURNED ON AND OFF BUT ORAL 709 00:33:58,103 --> 00:34:00,238 ADMINISTRATION OF THE SMALL 710 00:34:00,238 --> 00:34:01,206 MOLECULE DRUG. 711 00:34:01,206 --> 00:34:04,076 THE IDEA IS THEY INITIALLY KEEP 712 00:34:04,076 --> 00:34:06,778 THE EXPRESSION OFF TO ALLOW FOR 713 00:34:06,778 --> 00:34:09,948 IL12 EXPRESSION AND WE ADD THE 714 00:34:09,948 --> 00:34:11,616 SMALL MOLECULE TO TURN IT ON AND 715 00:34:11,616 --> 00:34:13,352 THEN KILL THE TUMOR AND RELEASE 716 00:34:13,352 --> 00:34:21,159 THE TUMOR ANTIGENS. 717 00:34:21,159 --> 00:34:24,863 THE REGULATED SIGNAL DEATH WE 718 00:34:24,863 --> 00:34:27,065 USE IS AN ANTIBIOTIC. 719 00:34:27,065 --> 00:34:34,239 IT'S BASED ON THIS D 720 00:34:34,239 --> 00:34:36,975 DE-ESTABLISHED DOMAIN AND THIS 721 00:34:36,975 --> 00:34:43,615 DD DOMAIN WHEN WE FUSE IT IT 722 00:34:43,615 --> 00:34:45,984 FORMS DEGRADATION AND FOR 723 00:34:45,984 --> 00:34:48,186 BINDING OF TMP STABILIZES THIS 724 00:34:48,186 --> 00:34:50,088 FUSION AND RESULTS IN EXPRESSION 725 00:34:50,088 --> 00:34:54,359 OF OUR GENE OF INTEREST. 726 00:34:54,359 --> 00:34:59,965 SO TO INCORPORATE THIS TMP 727 00:34:59,965 --> 00:35:03,735 RESPONSIVE GENE CIRCUIT IT TOOK 728 00:35:03,735 --> 00:35:05,470 TWO APPROACHES. 729 00:35:05,470 --> 00:35:07,406 IN THE DIRECT DD WE FUSED IT TO 730 00:35:07,406 --> 00:35:08,974 THE GENE OF INTEREST AND WHEN 731 00:35:08,974 --> 00:35:12,177 THERE'S NO TMP THE PROTEIN IS 732 00:35:12,177 --> 00:35:14,079 TODAY GRADED AFTER TRANSLATION 733 00:35:14,079 --> 00:35:15,614 AND GENE EXPRESSION IS TURNED 734 00:35:15,614 --> 00:35:18,450 OFF WHEN WE ADD THE TMP THE 735 00:35:18,450 --> 00:35:19,117 FUSION BECOMES STABLE AND GENE 736 00:35:19,117 --> 00:35:27,125 EXPRESSION IS TURNED ON. 737 00:35:27,125 --> 00:35:29,561 IN OUR SECOND APPROACH THE DD 738 00:35:29,561 --> 00:35:31,963 CIRCUIT APPROACH WE TARGET THE 739 00:35:31,963 --> 00:35:34,366 AMPLIFICATION MECHANISMS OF THE 740 00:35:34,366 --> 00:35:35,100 REPLICON. 741 00:35:35,100 --> 00:35:37,369 WE FUSE THE DD TO THE 742 00:35:37,369 --> 00:35:39,404 NON-STRUCTURAL PROTEINS OF THE 743 00:35:39,404 --> 00:35:40,338 REPLICON BACKBONE. 744 00:35:40,338 --> 00:35:44,009 WHEN THERE'S NO TMP THE COMPLEX 745 00:35:44,009 --> 00:35:48,413 IS DEGRADED AND REPLICON IS NOT 746 00:35:48,413 --> 00:35:49,381 ABLE TO REPLICATE AND WE LOSE IT 747 00:35:49,381 --> 00:35:50,348 AND THE RESULTING EXPRESSION IS 748 00:35:50,348 --> 00:35:54,019 OFF. 749 00:35:54,019 --> 00:35:56,054 IN THE PRESENCE OF TMP THE 750 00:35:56,054 --> 00:35:58,290 MACHINERY IS RESTORED AND THE 751 00:35:58,290 --> 00:35:59,591 REPLICON IS AMPLIFIES AND GENE 752 00:35:59,591 --> 00:36:05,764 EXPRESSION IS TURNED ON. 753 00:36:05,764 --> 00:36:10,969 AND WE CAN COMBINE THE 754 00:36:10,969 --> 00:36:14,339 APPROACHES AND CONNECT THEM TO 755 00:36:14,339 --> 00:36:16,675 THE GENE OF INTEREST. 756 00:36:16,675 --> 00:36:19,277 AND WE DESIGN DIFFERENT GENE 757 00:36:19,277 --> 00:36:22,747 CIRCUITS WITH DD FUSED THE FOUR 758 00:36:22,747 --> 00:36:23,982 NON-STRUCTURAL PROTEINS OF THE 759 00:36:23,982 --> 00:36:28,520 REM CON BACKBONE WITH OR WITHOUT 760 00:36:28,520 --> 00:36:30,355 AN ADDITIONAL DD FUSED GENE OF 761 00:36:30,355 --> 00:36:35,861 INTEREST. 762 00:36:35,861 --> 00:36:38,697 WE TESTED THE CIRCUIT IN VITRO 763 00:36:38,697 --> 00:36:41,666 AND LONG CANCER CELLS AND WITH 764 00:36:41,666 --> 00:36:45,704 THE EXCEPTION OF NSD4 WHERE THE 765 00:36:45,704 --> 00:36:51,776 FUSION ABOLISHES THE GENE 766 00:36:51,776 --> 00:36:54,012 EXPRESSION THE FUSION OF DD TO 767 00:36:54,012 --> 00:36:56,681 OTHER NSPs SHOWED AN EFFECTIVE 768 00:36:56,681 --> 00:36:58,350 STRATEGY FOR REGULATING THE GENE 769 00:36:58,350 --> 00:37:03,922 EXPRESSION. 770 00:37:03,922 --> 00:37:07,392 AND AMONG THE DIFFERENT GENE 771 00:37:07,392 --> 00:37:09,027 CIRCUITS WE DESIGN THE CIRCUIT 772 00:37:09,027 --> 00:37:15,700 TO BOAST NSP3 AND OUR GENE OF 773 00:37:15,700 --> 00:37:16,635 INTEREST SHOWED PROVIDE THE 774 00:37:16,635 --> 00:37:21,773 STRONGEST REGULATION WITH OVER 775 00:37:21,773 --> 00:37:25,010 100 FOLD DIFFERENCE IN THE BIO 776 00:37:25,010 --> 00:37:27,445 LUMINESCENCE SIGNAL BETWEEN ON 777 00:37:27,445 --> 00:37:31,016 AND OFF TMP STATES AND 778 00:37:31,016 --> 00:37:33,185 IMPORTANTLY THE OFF STATE THE 779 00:37:33,185 --> 00:37:37,022 EXPRESSION LEVEL WAS CLOSE TO 780 00:37:37,022 --> 00:37:38,323 THE BACKGROUND INDICATING NON 781 00:37:38,323 --> 00:37:43,461 EXPRESSION. 782 00:37:43,461 --> 00:37:45,630 WE ALSO DID TITRATION 783 00:37:45,630 --> 00:37:47,032 EXPERIMENTS AND SHOWED THE 784 00:37:47,032 --> 00:37:48,567 LEVELS OF THE GENE EXPRESSION 785 00:37:48,567 --> 00:37:51,002 CAN BE SUCCESSFULLY MODULATED BY 786 00:37:51,002 --> 00:37:56,775 VARYING THE OF IT TMP DOSE. 787 00:37:56,775 --> 00:38:00,145 WE CONTINUED WITH THE IN VIVO S 788 00:38:00,145 --> 00:38:06,318 AND HERE WE INJECTED REPLICONS 789 00:38:06,318 --> 00:38:07,819 INTERTEMPORALLY AND THE GENE 790 00:38:07,819 --> 00:38:11,523 EXPRESSION WAS MONITORED 791 00:38:11,523 --> 00:38:12,991 LONGITUDINALLY BY BIO 792 00:38:12,991 --> 00:38:13,658 LUMINESCENCE IMAGING. 793 00:38:13,658 --> 00:38:17,729 IN CASE OF THE CONSTITUTED 794 00:38:17,729 --> 00:38:20,999 REPLICON THE BIO LUMINESCENCE 795 00:38:20,999 --> 00:38:23,735 SIGNAL WAS SIMILAR WITH OR 796 00:38:23,735 --> 00:38:29,608 WITHOUT TMP AS EXPECTED BUT 797 00:38:29,608 --> 00:38:30,842 WITHOUT REGULATED CIRCUIT IN THE 798 00:38:30,842 --> 00:38:34,746 ABSENCE OF TMP THE SIGNAL WAS 799 00:38:34,746 --> 00:38:39,184 MINIMAL AND CLOSE TO BACKGROUND 800 00:38:39,184 --> 00:38:45,090 BUT WHEN WE ADD THE TMP IT 801 00:38:45,090 --> 00:38:45,657 SIGNIFICANTLY ELEVATED AND 802 00:38:45,657 --> 00:38:47,726 SHOWED LEVELS SIMILAR TO CLOSE 803 00:38:47,726 --> 00:38:58,270 TO THAT OF CONSTITUTED REPLICON. 804 00:38:58,470 --> 00:39:04,276 AND WE DESIGN GENE CIRCUITS AND 805 00:39:04,276 --> 00:39:07,412 THE FIRST GENE CIRCUIT WE DESIGN 806 00:39:07,412 --> 00:39:09,047 ACTUALLY FAILED AND WHEN WE LOOK 807 00:39:09,047 --> 00:39:14,452 AT THE CELL VIABILITY WE 808 00:39:14,452 --> 00:39:16,021 ACTUALLY SAW NO CYTOTOXICITY AND 809 00:39:16,021 --> 00:39:18,223 NO REGULATION. 810 00:39:18,223 --> 00:39:21,326 WE HYPOTHESIZED THIS MIGHT HAVE 811 00:39:21,326 --> 00:39:22,460 TO DO WITH THE DIFFERENCE 812 00:39:22,460 --> 00:39:24,663 BETWEEN DD AND GAS THERAPY. 813 00:39:24,663 --> 00:39:27,499 THE FIRST DESIGN WE HAD, WE HAD 814 00:39:27,499 --> 00:39:34,939 THE DD AT THE END TERMINIS AND 815 00:39:34,939 --> 00:39:36,474 USED THE LINK BETWEEN THE TWO. 816 00:39:36,474 --> 00:39:39,978 WE DESIGN DIFFERENT FUSIONS WITH 817 00:39:39,978 --> 00:39:42,213 DIFFERENT LINK SEQUENCES AND 818 00:39:42,213 --> 00:39:42,814 EXPERIMENTED WITH THE FUSION 819 00:39:42,814 --> 00:39:44,382 SITE OF DD. 820 00:39:44,382 --> 00:39:46,451 IN TERMS OF LINKER WE HAD THREE 821 00:39:46,451 --> 00:39:48,853 DIFFERENT LINKERS A LONG 822 00:39:48,853 --> 00:39:53,224 FLEXIBLE AND SHORT FLEXIBLE 823 00:39:53,224 --> 00:39:56,761 LINKER AND RIGID LINKER. 824 00:39:56,761 --> 00:39:59,264 AGAIN THE CIRCUITS WERE TESTED 825 00:39:59,264 --> 00:40:00,899 IN KP LONG CANCER CELLS AND 826 00:40:00,899 --> 00:40:06,004 FOUND IT WAS CRITICAL TO HAVE DD 827 00:40:06,004 --> 00:40:11,242 FUSED AT THE C TERMINIS AND 828 00:40:11,242 --> 00:40:13,044 AMONG THE LINKERS WE TEST THE 829 00:40:13,044 --> 00:40:18,950 SHORT FLEXIBLE LINKER AND THE 830 00:40:18,950 --> 00:40:21,052 RIGID LINKER PROVIDE GOOD 831 00:40:21,052 --> 00:40:23,154 REGULATION IN TERMS OF VIABILITY 832 00:40:23,154 --> 00:40:33,498 AND IL12 EXPRESSION. 833 00:40:34,766 --> 00:40:36,468 SO, FOR OUR THERAPEUTIC STUDY WE 834 00:40:36,468 --> 00:40:41,673 USED FUSION WITH A SHORT LINKER 835 00:40:41,673 --> 00:40:46,211 AND THE CIRCUIT WAS INJECTED 836 00:40:46,211 --> 00:40:50,782 INTERTUMORALLY AND TESTED THREE 837 00:40:50,782 --> 00:40:53,785 EXPRESSION PATTERNS HAVING THE 838 00:40:53,785 --> 00:40:55,587 EXPRESSION CONSTANTLY ON BY 839 00:40:55,587 --> 00:40:56,988 MAINTAINING TMP THROUGHOUT THE 840 00:40:56,988 --> 00:40:59,924 STUDY AND CONSTANTLY OFF BY 841 00:40:59,924 --> 00:41:03,728 REMOVING TMP THROUGHOUT OR 842 00:41:03,728 --> 00:41:05,163 KEEPING THE EXPRESSION OFF FOR 843 00:41:05,163 --> 00:41:07,465 TWO DAYS AND TURNING IT ON BY 844 00:41:07,465 --> 00:41:08,700 ADDING TMP. 845 00:41:08,700 --> 00:41:13,405 WE WERE HAPPY TO SEE THIS OFF/ON 846 00:41:13,405 --> 00:41:16,674 REGIMENT WAS ABLE TO ENHANCE THE 847 00:41:16,674 --> 00:41:22,347 THERAPEUTIC EFFICACY OF THIS TO 848 00:41:22,347 --> 00:41:29,521 THE IL GAS FORMULATION. 849 00:41:29,521 --> 00:41:32,424 TO SUMMARIZE WE HAVE ENGINEERED 850 00:41:32,424 --> 00:41:35,160 GENE CIRCUITS TO SMALL MOLECULE 851 00:41:35,160 --> 00:41:41,766 DRUG TRIMETHOPRENE AND HAVE 852 00:41:41,766 --> 00:41:47,705 INDUCTION OFFO GENIC -- 853 00:41:47,705 --> 00:41:49,140 IMMUNOGENIC CELL DEATHS AND BY 854 00:41:49,140 --> 00:41:55,046 DELAYING THIS WE CAN ENHANCE THE 855 00:41:55,046 --> 00:41:56,748 IL12 REPLICON. 856 00:41:56,748 --> 00:41:59,884 AND WITH THAT I WOULD LIKE TO 857 00:41:59,884 --> 00:42:04,155 THANK MY POSTDOC ADVISER AND ALL 858 00:42:04,155 --> 00:42:10,361 OTHER MEMBERS OF THE FLAG WHO 859 00:42:10,361 --> 00:42:16,067 CONTRIBUTED TO THE PROJECT AND 860 00:42:16,067 --> 00:42:18,036 AND FUNDING AGENCIES AND OF 861 00:42:18,036 --> 00:42:18,336 COURSE NIH. 862 00:42:18,336 --> 00:42:28,613 THANK YOU, GUYS. 863 00:42:30,782 --> 00:42:32,116 >> VERY NICE DATA. 864 00:42:32,116 --> 00:42:34,018 I'M CURIOUS ABOUT THE LENGTH OF 865 00:42:34,018 --> 00:42:39,491 THE REPLICON VERSUS THE DELIVERY 866 00:42:39,491 --> 00:42:39,791 EFFICIENCY. 867 00:42:39,791 --> 00:42:42,126 THE PIECE OF mRNA IS PRESUMABLY 868 00:42:42,126 --> 00:42:44,062 THE LESS COPIES YOU WOULD 869 00:42:44,062 --> 00:42:44,996 DELIVER INTO THE CELL AND 870 00:42:44,996 --> 00:42:48,233 CERTAINLY YOU WOULD GET THE 871 00:42:48,233 --> 00:42:48,900 AMPLIFICATION OVER TIME. 872 00:42:48,900 --> 00:42:50,602 AS I'M CURIOUS, YOU MUST HAVE 873 00:42:50,602 --> 00:42:52,136 SEEN SOME OF THOSE CHALLENGES 874 00:42:52,136 --> 00:42:54,072 AND CAN YOU COMMENT ON THE 875 00:42:54,072 --> 00:42:58,109 PLUSES AND MINUSES OF A LONGER 876 00:42:58,109 --> 00:43:01,012 REPLICON VERSUS A SHORTER PIECE 877 00:43:01,012 --> 00:43:02,814 OF mRNA THAT CANNOT REPLICATE 878 00:43:02,814 --> 00:43:05,316 BUT CAN DELIVER HIGHER DOSES AT 879 00:43:05,316 --> 00:43:05,583 THE ONSET. 880 00:43:05,583 --> 00:43:12,524 >> SO, THAT'S A GOOD POINT BUT 881 00:43:12,524 --> 00:43:23,635 FOR OUR BIO ILLUILLUMOESSENCE A 882 00:43:24,302 --> 00:43:27,338 REPLICONS ALLOW FOR LONG-LASTING 883 00:43:27,338 --> 00:43:28,506 GENE EXPRESSION AS WITH mRNA 884 00:43:28,506 --> 00:43:30,308 EXPRESSION ONLY LASTS A FEW 885 00:43:30,308 --> 00:43:31,142 DAYS. 886 00:43:31,142 --> 00:43:35,780 EVEN WITH A HIGHER DOSE USING 887 00:43:35,780 --> 00:43:37,415 mRNA REPLICON STILL PROVIDES 888 00:43:37,415 --> 00:43:39,450 THE, I GUESS, WINS. 889 00:43:39,450 --> 00:43:40,585 >> GOOD MORNING. 890 00:43:40,585 --> 00:43:41,553 THANK YOU VERY MUCH FOR THE 891 00:43:41,553 --> 00:43:42,287 PRESENTATION. 892 00:43:42,287 --> 00:43:47,458 IT'S A WONDERFUL SYSTEM. 893 00:43:47,458 --> 00:43:52,697 IN THE LUCIFERASE EXPRESSION AND 894 00:43:52,697 --> 00:43:53,965 OF THE SIGNAL THAT'S WITH THE 895 00:43:53,965 --> 00:43:56,701 SYSTEM WITH THE TWO DD SYSTEMS 896 00:43:56,701 --> 00:43:58,336 IN IT. 897 00:43:58,336 --> 00:43:58,903 THE PROFILE THE EXPRESSION 898 00:43:58,903 --> 00:44:01,005 DIFFERENT IF YOU JUST USE ONE OR 899 00:44:01,005 --> 00:44:02,340 THE OTHER? 900 00:44:02,340 --> 00:44:03,775 IT'S INTERESTING HOW IT GOES UP 901 00:44:03,775 --> 00:44:04,409 A LITTLE BIT AND A LITTLE BIT 902 00:44:04,409 --> 00:44:05,777 MORE AND THEN BACK DOWN. 903 00:44:05,777 --> 00:44:07,445 DO YOU HAVE ENOUGH DATA TO SEE 904 00:44:07,445 --> 00:44:10,748 HOW THE DIFFERENT ANALOGS MIGHT 905 00:44:10,748 --> 00:44:12,317 GIVE DIFFERENT EXPRESSION 906 00:44:12,317 --> 00:44:12,584 PATTERNS? 907 00:44:12,584 --> 00:44:16,387 >> YEAH, THANK YOU FOR THE 908 00:44:16,387 --> 00:44:16,654 QUESTION. 909 00:44:16,654 --> 00:44:18,957 SO WE ACTUALLY INITIALLY STARTED 910 00:44:18,957 --> 00:44:21,826 WITH THE DIRECT DD CIRCUIT AND 911 00:44:21,826 --> 00:44:23,161 HAD IT FUSE TO OUR GENE OF 912 00:44:23,161 --> 00:44:26,931 INTEREST AND THEN THAT ONE WAS 913 00:44:26,931 --> 00:44:27,398 SUPER IN VIVO. 914 00:44:27,398 --> 00:44:30,635 THAT'S WHY WE WENT BACK TO LIKE 915 00:44:30,635 --> 00:44:32,870 DESIGN BOARD AND THEN WE CAME UP 916 00:44:32,870 --> 00:44:35,006 WITH THE STRATEGY OF HAVING THE 917 00:44:35,006 --> 00:44:42,213 DD ALSO FUSE TO NSBs. 918 00:44:42,213 --> 00:44:43,014 >> ANY OTHER QUESTION? 919 00:44:43,014 --> 00:44:53,191 THANK YOU. 920 00:44:53,424 --> 00:44:54,959 >> THANK YOU FOR THIS MORNING'S 921 00:44:54,959 --> 00:44:55,360 SPEAKERS. 922 00:44:55,360 --> 00:44:57,495 WE'RE GOING TO BREAK FOR 30 923 00:44:57,495 --> 00:45:01,599 MINUTES SO COFFEE AND SOME 924 00:45:01,599 --> 00:45:02,266 PASTRIES ARE IN THE ROOM ACROSS 925 00:45:02,266 --> 00:45:02,500 FROM US. 926 00:45:02,500 --> 00:45:04,866 THANK YOU. 927 00:45:04,866 --> 00:45:07,302 LIKE TO INTRODUCE OUR NEXT 928 00:45:07,302 --> 00:45:14,108 SPEAKER, DR. BORHANI AND GROWS 929 00:45:14,108 --> 00:45:14,976 GINKO OPPORTUNITIES IN THE 930 00:45:14,976 --> 00:45:18,579 GOVERNMENT AND LED TEAMS TO WIN 931 00:45:18,579 --> 00:45:21,983 THE LARGEST GOVERNMENT AWARDS 932 00:45:21,983 --> 00:45:23,952 INCLUDING PRE-CELL THERAPEUTIC 933 00:45:23,952 --> 00:45:30,792 SYNTHESIS FROM DARPAR AND 934 00:45:30,792 --> 00:45:33,962 SECURED AN NIH RADX AWARD FOR A 935 00:45:33,962 --> 00:45:36,597 TESTING PROGRAM AND HELPED GINKO 936 00:45:36,597 --> 00:45:37,765 EXPAND INTO BIO SECURITY. 937 00:45:37,765 --> 00:45:42,136 HE WON GINKO'S FIRST PHARMA 938 00:45:42,136 --> 00:45:44,706 CONTRACT WITH LILY AND INITIATED 939 00:45:44,706 --> 00:45:55,116 AND CO-LED THE ONE WITH 940 00:46:00,188 --> 00:46:04,592 NOVONORDIS AND GOT HIS Ph.D. 941 00:46:04,592 --> 00:46:05,360 FROM M.I.T. 942 00:46:05,360 --> 00:46:15,837 WELCOME TO THE STAGE, DAVID. 943 00:46:18,439 --> 00:46:19,907 >> THANK YOU FOR THE INVITATION 944 00:46:19,907 --> 00:46:20,675 TO SPEAK HERE TODAY. 945 00:46:20,675 --> 00:46:23,277 WHAT A WANTED TO TELL YOU ABOUT 946 00:46:23,277 --> 00:46:25,980 TODAY IS GINKO'S CELL 947 00:46:25,980 --> 00:46:27,582 PROGRAMMING PLATFORM. 948 00:46:27,582 --> 00:46:29,050 WHERE WE STARTED AND WHAT IT 949 00:46:29,050 --> 00:46:30,651 LOOKS LIKE AND WHAT IT'S LIKE TO 950 00:46:30,651 --> 00:46:32,653 RUN ON THE PLATFORM AND WHERE WE 951 00:46:32,653 --> 00:46:34,722 THINK WE'RE GOING. 952 00:46:34,722 --> 00:46:38,026 AND GIVE YOU SOME EXAMPLES 953 00:46:38,026 --> 00:46:39,494 MOSTLY FROM THE PHARMA SPACE. 954 00:46:39,494 --> 00:46:43,664 THERE'S ONE I HOPE TO GET TO AT 955 00:46:43,664 --> 00:46:44,365 THE END THAT WILL PREP US FOR 956 00:46:44,365 --> 00:46:54,142 LUNCH. 957 00:46:54,142 --> 00:46:55,676 OKAY. 958 00:46:55,676 --> 00:46:59,881 SO, GINKO STARTED 15 YEARS AGO 959 00:46:59,881 --> 00:47:02,583 AND ON THE LEFT SIDE YOU SEE ONE 960 00:47:02,583 --> 00:47:06,387 OF OUR FIVE FOUNDERS, TOM 961 00:47:06,387 --> 00:47:06,621 KNIGHT. 962 00:47:06,621 --> 00:47:10,458 TOM WAS A PROFESSOR IN THE 963 00:47:10,458 --> 00:47:10,958 ELECTRICAL ENGINEERING 964 00:47:10,958 --> 00:47:14,328 DEPARTMENT AT M.I.T. 965 00:47:14,328 --> 00:47:19,567 HAD, HAD AT THAT POINT A LONG 966 00:47:19,567 --> 00:47:20,268 CAREER PROGRAMMING COMPUTERS AND 967 00:47:20,268 --> 00:47:23,938 I'M BLANKING ON THE NAME OF THE 968 00:47:23,938 --> 00:47:34,449 PERSON WITH HIM THERE. 969 00:47:34,449 --> 00:47:36,651 THEY'RE PROGRAMMING A MINI 970 00:47:36,651 --> 00:47:36,918 COMPUTER. 971 00:47:36,918 --> 00:47:39,387 HOW TIMES HAVE CHANGE. 972 00:47:39,387 --> 00:47:41,089 AND TOM WANTED TO DO EXPECT 973 00:47:41,089 --> 00:47:43,925 DIFFERENT THAN PROGRAMMING 974 00:47:43,925 --> 00:47:47,829 SILICON AS TIME WENT ON AND THE 975 00:47:47,829 --> 00:47:52,633 CELLS BIOLOGY WAS NOTHING BUT A 976 00:47:52,633 --> 00:47:54,068 COMPUTER RUNNING ON CODE LIKE 977 00:47:54,068 --> 00:47:57,972 THE SILICON COMPUTER AND NOT 978 00:47:57,972 --> 00:48:04,779 RUNNING ON 1s AND 0s BUT As, Gs 979 00:48:04,779 --> 00:48:07,215 AND Ts AND WENT BACK TO GRADUATE 980 00:48:07,215 --> 00:48:08,950 SCHOOL AND STARTED UP A LAB 981 00:48:08,950 --> 00:48:11,853 DOING BIOLOGY AND THE REST IS 982 00:48:11,853 --> 00:48:12,086 HISTORY. 983 00:48:12,086 --> 00:48:16,924 AND ALSO SHOWN ON THE RIGHT SIDE 984 00:48:16,924 --> 00:48:22,363 THEN ARE OTHER FOUR CO-FOUNDERS, 985 00:48:22,363 --> 00:48:26,801 ARI, JASON, RUSHMA AND OSMAN ALL 986 00:48:26,801 --> 00:48:30,538 STILL WITH GINKO, CEO, COO, 987 00:48:30,538 --> 00:48:33,708 CHIEF TECHNOLOGY OFFICER, I 988 00:48:33,708 --> 00:48:36,310 GUESS IS HIS TITLE AND STRATEGY 989 00:48:36,310 --> 00:48:37,745 IS WHAT AUSTIN DOES. 990 00:48:37,745 --> 00:48:39,147 AND A RECENT PICTURE FROM JUST A 991 00:48:39,147 --> 00:48:41,782 COUPLE YEARS AGO. 992 00:48:41,782 --> 00:48:43,918 AND YOU CAN GET A GLIMPSE OF 993 00:48:43,918 --> 00:48:46,721 WHAT OUR BUILDING LOOKS LIKE ON 994 00:48:46,721 --> 00:48:47,188 THE INSIGHT. 995 00:48:47,188 --> 00:48:50,758 -- INSIDE. 996 00:48:50,758 --> 00:48:52,627 SO JUST A LITTLE BIT MORE DETAIL 997 00:48:52,627 --> 00:48:53,694 ABOUT GINKO. 998 00:48:53,694 --> 00:48:57,732 WE'RE A PUBLIC COMPANY. 999 00:48:57,732 --> 00:49:03,905 WE WENT PUBLIC IN 2021. 1000 00:49:03,905 --> 00:49:06,741 TIME FLIES, COVID AND ALL. 1001 00:49:06,741 --> 00:49:09,911 AND HOW WE'VE POSITIONED 1002 00:49:09,911 --> 00:49:13,514 OURSELVES IS AS AN INNOVATION 1003 00:49:13,514 --> 00:49:14,916 PARTNER FOR BOTH THE COMMERCIAL 1004 00:49:14,916 --> 00:49:16,717 SPACE AND GOVERNMENT SPACE. 1005 00:49:16,717 --> 00:49:18,286 AND WE'RE WORKING ACROSS 1006 00:49:18,286 --> 00:49:20,922 INDUSTRIES AND IN PHARMA IN 1007 00:49:20,922 --> 00:49:21,689 PARTICULAR WE'RE WORKING ACROSS 1008 00:49:21,689 --> 00:49:22,523 THERAPEUTIC MODALITIES. 1009 00:49:22,523 --> 00:49:26,928 I'LL TELL YOU MORE ABOUT THAT. 1010 00:49:26,928 --> 00:49:30,865 SO OVER THE LAST 15 YEARS WE'VE 1011 00:49:30,865 --> 00:49:34,702 JUST BEEN BUILDING A LARGE OUT 1012 00:49:34,702 --> 00:49:37,538 MATED PLATFORM AND THE SOFTWARE 1013 00:49:37,538 --> 00:49:39,807 NEEDED TO RUN IT AND THE 1014 00:49:39,807 --> 00:49:41,642 CODE-BASE ON WHICH IT RUNS IN 1015 00:49:41,642 --> 00:49:47,248 ORDER TO ENABLE JUST EVER MORE 1016 00:49:47,248 --> 00:49:48,115 APPLICATIONS IN SYNTHETIC 1017 00:49:48,115 --> 00:49:48,616 BIOLOGY. 1018 00:49:48,616 --> 00:49:50,851 AND A BIG PUSH IN THE PHARMA 1019 00:49:50,851 --> 00:49:53,688 AREA AND WE BROUGHT ON TO OUR 1020 00:49:53,688 --> 00:49:58,626 BOARD A COUPLE YEAR AGO, BARE 1021 00:49:58,626 --> 00:50:02,196 REGELDMAN FROM KITE AND RUSHMAN 1022 00:50:02,196 --> 00:50:03,497 ROMANI FROM VERTEX. 1023 00:50:03,497 --> 00:50:07,635 SO PHARMA APPLICATIONS ACTUALLY 1024 00:50:07,635 --> 00:50:10,738 REPRESENT A BIT OVER 50% OF WHAT 1025 00:50:10,738 --> 00:50:14,942 GINKO DOES AND YOU'LL SEE ON THE 1026 00:50:14,942 --> 00:50:19,914 NEXT SLIDE EVERYTHING ELSE WE'RE 1027 00:50:22,984 --> 00:50:23,217 IN. 1028 00:50:23,217 --> 00:50:26,287 AND DURING COVID WE STOOD UP A 1029 00:50:26,287 --> 00:50:32,360 WHOLE BIO SECURITY UNIT CALLED 1030 00:50:32,360 --> 00:50:32,660 CO-CENTRIC. 1031 00:50:32,660 --> 00:50:34,428 HALF IS PHARMA AND HALF IN BIO 1032 00:50:34,428 --> 00:50:35,896 AND THE OTHER HALF AND THAT'S 1033 00:50:35,896 --> 00:50:39,600 CONCENTRIC. 1034 00:50:39,600 --> 00:50:43,638 AND WE HAD STOOD UP AN ENTIRE 1035 00:50:43,638 --> 00:50:45,640 TESTING NETWORK AND NOW 1036 00:50:45,640 --> 00:50:46,440 EXPANDING INTERNATIONALLY. 1037 00:50:46,440 --> 00:50:50,478 SO THIS IS MY FAVORITE SLIDE I 1038 00:50:50,478 --> 00:50:53,047 EVER SHOW BECAUSE IT KIND OF 1039 00:50:53,047 --> 00:50:55,583 ENCAPSULATES IN A COMPLETE 1040 00:50:55,583 --> 00:50:55,916 NUTSHELL. 1041 00:50:55,916 --> 00:50:59,487 WE ARE WORKING WITH LARGE 1042 00:50:59,487 --> 00:51:00,755 COMPANIES UP AT THE TOP. 1043 00:51:00,755 --> 00:51:11,299 START UPS AT THE BOTTOM PHARMA 1044 00:51:13,267 --> 00:51:14,235 AND WELLNESS IN FOOD AND 1045 00:51:14,235 --> 00:51:15,236 AGRICULTURE AND THERE'S A 1046 00:51:15,236 --> 00:51:18,105 TRANSITION FROM PHARMA AND 1047 00:51:18,105 --> 00:51:19,140 ENDING UP AT INDUSTRIAL BIO TECH 1048 00:51:19,140 --> 00:51:21,075 AT THE RIGHT SIDE. 1049 00:51:21,075 --> 00:51:23,344 IT'S JUST I COULD SPEND AN HOUR 1050 00:51:23,344 --> 00:51:24,545 TALKING ABOUT EACH ONE OF THESE 1051 00:51:24,545 --> 00:51:25,713 COMPANIES AND WHAT WE'RE DOING 1052 00:51:25,713 --> 00:51:28,382 BUT IF I WERE TO JUST HIGHLIGHT 1053 00:51:28,382 --> 00:51:31,652 A COUPLE OF THEM, RECENT 1054 00:51:31,652 --> 00:51:32,687 ANNOUNCEMENT OF A VERY LARGE 1055 00:51:32,687 --> 00:51:38,926 DEAL WITH PFIZER TO DEVELOP 1056 00:51:38,926 --> 00:51:40,895 RNA-BASED THERAPEUTICS. 1057 00:51:40,895 --> 00:51:51,439 WE MENTIONED LILLY AS AN ENZYME 1058 00:51:52,606 --> 00:51:56,544 DEALER AND BIO GEN WE'VE BEEN 1059 00:51:56,544 --> 00:52:01,549 WORKING ON AAV MANUFACTURING 1060 00:52:01,549 --> 00:52:09,056 WITH THEM AND ANTHEIA AND IT'S A 1061 00:52:09,056 --> 00:52:11,359 COMPANY SPUN OUT AND FORMED FROM 1062 00:52:11,359 --> 00:52:14,195 THE PLATFORM AND BRING IN 1063 00:52:14,195 --> 00:52:15,329 VENTURE INVESTORS THAT CAN 1064 00:52:15,329 --> 00:52:17,298 PROVIDE SOME OF THE CAPITAL. 1065 00:52:17,298 --> 00:52:21,635 GINKO PROVIDES THE PLATFORM ON 1066 00:52:21,635 --> 00:52:24,405 WHICH THESE COMPANIES' PROGRAMS 1067 00:52:24,405 --> 00:52:27,908 RUN AND ANTHIA MAKE DRUGS THAT 1068 00:52:27,908 --> 00:52:30,544 TYPICALLY COME FROM PLANT BUT 1069 00:52:30,544 --> 00:52:31,712 INSTEAD USING SYNTHETIC BIOLOGY 1070 00:52:31,712 --> 00:52:32,947 AND THE POWER OF THE PLATFORM TO 1071 00:52:32,947 --> 00:52:38,552 MAKE THAT HAPPEN. 1072 00:52:38,552 --> 00:52:38,953 OKAY. 1073 00:52:38,953 --> 00:52:46,460 AND WE HAVE A FAIR AMOUNT OF 1074 00:52:46,460 --> 00:52:51,565 GOVERNMENT FUNDING. 1075 00:52:51,565 --> 00:52:54,535 WHAT WE USE GOVERNMENT FUNDING 1076 00:52:54,535 --> 00:52:56,437 FOR IS TO PUSH THE BOUNDARIES OF 1077 00:52:56,437 --> 00:52:59,874 WHAT'S POSSIBLE AND YOU SEE THE 1078 00:52:59,874 --> 00:53:01,442 DARPA LABEL AND WOULD LOVE TO 1079 00:53:01,442 --> 00:53:02,510 EXPAND TO OTHER AGENCIES. 1080 00:53:02,510 --> 00:53:04,545 AND I FORGOT TO PUT IT ON THERE 1081 00:53:04,545 --> 00:53:05,913 BUT RECENTLY ANNOUNCED AWARD 1082 00:53:05,913 --> 00:53:09,283 THAT GINKO'S PART OF WITH THE 1083 00:53:09,283 --> 00:53:11,919 USDA WHICH IS OUR FIRST WITH 1084 00:53:11,919 --> 00:53:17,992 THEM. 1085 00:53:17,992 --> 00:53:20,094 WHY ARE PEOPLE WORKING WITH 1086 00:53:20,094 --> 00:53:20,361 GINKO? 1087 00:53:20,361 --> 00:53:25,266 WE HAVE THE INNOVATION AND BRING 1088 00:53:25,266 --> 00:53:27,101 THE CAPABILITIES THEY WOULD LIKE 1089 00:53:27,101 --> 00:53:28,836 TO HAVE IN HOUSE BUT DON'T WANT 1090 00:53:28,836 --> 00:53:30,070 TO TAKE THE TIME AND EXPENSE TO 1091 00:53:30,070 --> 00:53:30,838 DO IT. 1092 00:53:30,838 --> 00:53:36,510 SO IF YOU THINK ABOUT LIKE WHAT 1093 00:53:36,510 --> 00:53:44,385 IT TAKES TO MOVE INTO A NEW AREA 1094 00:53:44,385 --> 00:53:45,686 IT'S A BIG DEAL. 1095 00:53:45,686 --> 00:53:47,721 YOU HAVE TO ALLOCATE THE 1096 00:53:47,721 --> 00:53:52,660 LABORATORY RESOURCES AND WHO 1097 00:53:52,660 --> 00:53:55,429 WILL LEAD IT AND HIRE. 1098 00:53:55,429 --> 00:53:57,798 SO IT'S A LONG START-UP TIME AND 1099 00:53:57,798 --> 00:53:59,166 WHAT DO YOU DO THREE YEARS LATER 1100 00:53:59,166 --> 00:54:00,935 IF YOU THINK IT'S NOT A GREAT 1101 00:54:00,935 --> 00:54:02,636 IDEA AND NEED TO DO SOMETHING 1102 00:54:02,636 --> 00:54:03,404 ELSE INSTEAD? 1103 00:54:03,404 --> 00:54:04,538 WHERE A COMPANY LIKE GINKO COMES 1104 00:54:04,538 --> 00:54:06,307 IN AND THIS APPLIES TO 1105 00:54:06,307 --> 00:54:08,476 COMMERCIAL COMPANIES AND THE 1106 00:54:08,476 --> 00:54:11,111 GOVERNMENT AS WELL IS WE HAVE 1107 00:54:11,111 --> 00:54:16,050 THE INFRASTRUCTURE BUILT. 1108 00:54:16,050 --> 00:54:18,786 IT'S ABLE TO RUN MANY PROGRAMS 1109 00:54:18,786 --> 00:54:19,153 SIMULTANEOUSLY. 1110 00:54:19,153 --> 00:54:21,021 I THINK WE HAVE 100 CURRENT 1111 00:54:21,021 --> 00:54:25,025 PROJECTS RUNNING AT THE SAME 1112 00:54:25,025 --> 00:54:26,360 TIME AND STOP AND START AND 1113 00:54:26,360 --> 00:54:29,930 BRING IN SOMETHING NEW THAT 1114 00:54:29,930 --> 00:54:30,764 REALLY CAN GET YOU GOING 1115 00:54:30,764 --> 00:54:31,532 QUICKLY. 1116 00:54:31,532 --> 00:54:34,635 I HAVE A SLIDE I DIDN'T PUT ON 1117 00:54:34,635 --> 00:54:36,170 HERE THAT SORT OF SHOWS THAT 1118 00:54:36,170 --> 00:54:37,605 GRAPHICALLY BUT YOU'D LIKE TO BE 1119 00:54:37,605 --> 00:54:38,939 ABLE TO TURN ON AND TURN OFF AND 1120 00:54:38,939 --> 00:54:45,479 THIS IS ESPECIALLY TRUE FOR 1121 00:54:45,479 --> 00:54:50,284 SMALLER COMPANIES SAY SMALL 1122 00:54:50,284 --> 00:54:54,722 START-UP COMPANIES AND WANT TO 1123 00:54:54,722 --> 00:54:55,956 PUSH AS HARD AS YOU CAN INTO A 1124 00:54:55,956 --> 00:54:58,192 PLATFORM LIKE GINKO. 1125 00:54:58,192 --> 00:55:02,029 I WANT TO TEST TENS OF THOUSANDS 1126 00:55:02,029 --> 00:55:05,266 OF MY DESIGN AAV OR BIOLOGIC OR 1127 00:55:05,266 --> 00:55:06,033 WHATEVER IT IS AND YOU'RE 1128 00:55:06,033 --> 00:55:08,836 SUCCESSFUL AND YOU GO TO THE 1129 00:55:08,836 --> 00:55:10,771 CLINIC AND ALL YOUR TIME AND 1130 00:55:10,771 --> 00:55:12,673 MONEY AND EFFORT IS FOCUSSED ON 1131 00:55:12,673 --> 00:55:13,908 THE CLINICAL TRIALS AND YOU'VE 1132 00:55:13,908 --> 00:55:15,910 GOT TO GET TO THAT FIRST WIN 1133 00:55:15,910 --> 00:55:17,711 BEFORE THEN YOU CAN START YOUR 1134 00:55:17,711 --> 00:55:19,346 BACK UP PROGRAMS. 1135 00:55:19,346 --> 00:55:21,615 IT'S LIKE THIS BOOM AND THEN 1136 00:55:21,615 --> 00:55:23,617 BUST IN TERMS OF THE R&D 1137 00:55:23,617 --> 00:55:23,951 LABORATORIES. 1138 00:55:23,951 --> 00:55:24,618 SO GINKO CAN HELP SMOOTH THAT 1139 00:55:24,618 --> 00:55:28,088 OUT. 1140 00:55:28,088 --> 00:55:29,924 OKAY. 1141 00:55:29,924 --> 00:55:33,093 SOME VERY NICE WORDS FROM FOLKS 1142 00:55:33,093 --> 00:55:41,969 AT NOVO NORDISK. 1143 00:55:41,969 --> 00:55:44,505 IF YOU LOOK AT THE PRESS 1144 00:55:44,505 --> 00:55:46,340 RELEASES AND I HAVE TO BE 1145 00:55:46,340 --> 00:55:48,676 CAREFUL WHAT I SAY HERE. 1146 00:55:48,676 --> 00:55:50,210 IT'S ABOUT MANUFACTURING IN 1147 00:55:50,210 --> 00:55:51,312 MICROORGANISMS AND EXPANDING THE 1148 00:55:51,312 --> 00:55:55,916 CHEMICAL UNIVERSE AND YOU ALL 1149 00:55:55,916 --> 00:56:03,090 CAN READ BETWEEN THE LINES. 1150 00:56:03,090 --> 00:56:07,628 WE HAD A BIG WILL PROGRAM AND 1151 00:56:07,628 --> 00:56:09,863 BAYER SAID YOU GUYS ARE DOING 1152 00:56:09,863 --> 00:56:11,765 GREAT AND LET'S MOVE THAT TO 1153 00:56:11,765 --> 00:56:14,969 GINKO AND LET'S CONTINUE THE 1154 00:56:14,969 --> 00:56:17,605 COLLABORATION AND AS A RESULT OF 1155 00:56:17,605 --> 00:56:21,308 THAT GINKO ACQUIRED GREENHOUSE 1156 00:56:21,308 --> 00:56:21,976 FACILITIES IN CALIFORNIA AND A 1157 00:56:21,976 --> 00:56:23,978 PROJECT THAT GOES UP TO 3,000 1158 00:56:23,978 --> 00:56:25,012 LITER. 1159 00:56:25,012 --> 00:56:29,883 I'LL FINISH WITH THIS NOTE FROM 1160 00:56:29,883 --> 00:56:32,119 BRYAN VANDAL ABOUT THE FUTURE OF 1161 00:56:32,119 --> 00:56:33,287 A.I. IN BIOLOGY AND MIKE TOUCHED 1162 00:56:33,287 --> 00:56:38,792 ON THIS AT THEN OF HIS TALK AND 1163 00:56:38,792 --> 00:56:40,394 INDEED THIS IS WHERE WE'RE 1164 00:56:40,394 --> 00:56:41,428 GOING. 1165 00:56:41,428 --> 00:56:47,167 WE ANNOUNCED JUST AT THE END OF 1166 00:56:47,167 --> 00:56:47,901 AUGUST A RELATIONSHIP WITH 1167 00:56:47,901 --> 00:56:49,837 GOOGLE CLOUD WHERE WE HAVE 1168 00:56:49,837 --> 00:56:53,240 PREFERENTIAL ACCESS TO THEIR 1169 00:56:53,240 --> 00:56:57,244 PROCESSING UNITS PRECISELY TO DO 1170 00:56:57,244 --> 00:56:58,812 THIS TO LEVERAGE THE AMAZING 1171 00:56:58,812 --> 00:56:59,913 AMOUNT OF DATA GINKO HAS 1172 00:56:59,913 --> 00:57:01,715 GATHERED OVER THE YEARS AND 1173 00:57:01,715 --> 00:57:02,950 ABILITY TO GATHER MORE DATA IN 1174 00:57:02,950 --> 00:57:06,420 THE BIOLOGICAL REALM AND REALLY 1175 00:57:06,420 --> 00:57:08,188 TRANSFORM HOW IT IS WE'RE DOING 1176 00:57:08,188 --> 00:57:10,691 THESE KINDS OF DESIGNS IN THE 1177 00:57:10,691 --> 00:57:13,260 PROTEIN SPACE, IN THE DNA, RNA 1178 00:57:13,260 --> 00:57:14,962 SPACE IN THE BIO SECURITY SPACE 1179 00:57:14,962 --> 00:57:20,367 AS WELL. 1180 00:57:20,367 --> 00:57:22,569 I REALIZE I HAVE NO PICTURES OF 1181 00:57:22,569 --> 00:57:23,303 OUR LABORATORY. 1182 00:57:23,303 --> 00:57:27,641 THIS IS AN OLD PICTURE BUT GIVES 1183 00:57:27,641 --> 00:57:29,610 A SENSE OF HOW MANY ROBOTS AND I 1184 00:57:29,610 --> 00:57:30,811 DON'T KNOW HOW MANY AT THIS 1185 00:57:30,811 --> 00:57:35,049 POINT AND THE WHOLE POINT IS TO 1186 00:57:35,049 --> 00:57:36,850 AUTOMATE THE UNIT OPERATIONS 1187 00:57:36,850 --> 00:57:41,889 THAT TAKE PLACE AS YOU'RE 1188 00:57:41,889 --> 00:57:44,692 ENGINEERING AN ORGANISM. 1189 00:57:44,692 --> 00:57:46,560 BOTH AT THE DESIGN STAGE AND 1190 00:57:46,560 --> 00:57:49,797 HAVE SET PROGRAM PACKAGES THAT 1191 00:57:49,797 --> 00:58:00,240 IF YOU NEED TO GO DESIGN 1192 01:04:13,513 --> 01:04:16,550 AAV 9 IN BLUE AND ON THE LEFT 1193 01:04:16,550 --> 01:04:20,921 SIDE WE HAVE CAPSIDS THAT HAVE 1194 01:04:20,921 --> 01:04:23,690 BEEN VALIDATED IN NON-HUMAN 1195 01:04:23,690 --> 01:04:23,957 PRIMATES. 1196 01:04:23,957 --> 01:04:25,792 ON THE RIGHT ARE THE EARLIER 1197 01:04:25,792 --> 01:04:36,336 ONES IN MICE OR PERHAPS STILL IN 1198 01:04:46,246 --> 01:04:47,514 VITRO CAPSID AND THIS THE 1199 01:04:47,514 --> 01:04:50,016 PASSAGING PROCESS. 1200 01:04:50,016 --> 01:04:52,252 MAKE THE LIBRARIES SO 47 STARTED 1201 01:04:52,252 --> 01:04:53,286 WITH AAV 9. 1202 01:04:53,286 --> 01:04:56,523 ALL KINDS OF VARIANTS WENT INTO 1203 01:04:56,523 --> 01:05:00,927 PIGS AND THE WINNERS ARE AT THE 1204 01:05:00,927 --> 01:05:03,096 TOP OF THAT PANEL AND IT'S HOW 1205 01:05:03,096 --> 01:05:04,464 PREVALENT ARE THE READS IN A 1206 01:05:04,464 --> 01:05:07,734 GIVEN TISSUE AND THE SIZE OF THE 1207 01:05:07,734 --> 01:05:09,136 BUBBLES ARE HOW MUCH OF AN 1208 01:05:09,136 --> 01:05:10,737 INCREASE WAS THAT OVER WHERE 1209 01:05:10,737 --> 01:05:15,142 THAT PARTICULAR CAPSID STARTED. 1210 01:05:15,142 --> 01:05:16,643 AND THEN THE WINNERS IN THE PIG 1211 01:05:16,643 --> 01:05:18,912 WENT INTO THE MOUSE AND THE 1212 01:05:18,912 --> 01:05:21,148 WINNERS IN THE MOUSE WENT INTO 1213 01:05:21,148 --> 01:05:23,950 THE MONKEYS AND THAT BIG ONE AT 1214 01:05:23,950 --> 01:05:31,558 THE TOP IS NUMBER 47. 1215 01:05:31,558 --> 01:05:35,328 WE CAN THINK OF IT AS AN AAV9 1216 01:05:35,328 --> 01:05:39,499 WITH INTERESTING MUTATIONS AND 1217 01:05:39,499 --> 01:05:43,003 WHAT THEY DO IS THEY LET IT GO 1218 01:05:43,003 --> 01:05:46,840 TO MANY OF THE SAME TISSUES THAT 1219 01:05:46,840 --> 01:05:48,441 AAV 9 DOES GIVES HIGHER 1220 01:05:48,441 --> 01:05:48,975 EXPRESSION. 1221 01:05:48,975 --> 01:05:51,678 THAT'S SHOWN IN THESE DATA 1222 01:05:51,678 --> 01:05:53,146 GRAPHS ACROSS DIFFERENT TISSUES 1223 01:05:53,146 --> 01:05:59,019 AND IN THE IMAGES IN THE 1224 01:05:59,019 --> 01:05:59,853 IMMUNOHISTO CHEMISTRY. 1225 01:05:59,853 --> 01:06:07,160 AND THAT ONE WAS IN MICE AND 1226 01:06:07,160 --> 01:06:09,129 THIS IS IN MONKEYS INJECTED INTO 1227 01:06:09,129 --> 01:06:11,932 THE BRAIN OF THE MONKEYS AND YOU 1228 01:06:11,932 --> 01:06:17,437 CAN SEE 47 IS LIGHTING UP ON THE 1229 01:06:17,437 --> 01:06:19,606 RIGHT SIDE. 1230 01:06:19,606 --> 01:06:21,141 INTERESTINGLY IT SHOWS MUCH 1231 01:06:21,141 --> 01:06:25,445 HIGHER EXPRESSION IN THE KIDNEY. 1232 01:06:25,445 --> 01:06:28,982 AND THAT'S SHOWN ON THE RIGHT 1233 01:06:28,982 --> 01:06:34,120 PANEL AND QUANTITATIVELY THEN 1234 01:06:34,120 --> 01:06:37,924 OVER HERE THE WIDER SPREADING OF 1235 01:06:37,924 --> 01:06:47,000 THE GENE DELIVERY IN THE KIDNEY. 1236 01:06:47,000 --> 01:06:49,536 SO WHAT DO YOU DO WITH A CAPSID 1237 01:06:49,536 --> 01:06:51,638 LIKE 47 WORKING BETTER BUT GOING 1238 01:06:51,638 --> 01:06:52,639 TO DIFFERENT TISSUES? 1239 01:06:52,639 --> 01:06:54,007 HOW DO YOU GET SPECIFIC THERAPY? 1240 01:06:54,007 --> 01:06:55,642 THIS IS ANOTHER PLACE WHERE THE 1241 01:06:55,642 --> 01:06:57,043 GINKO PLATFORM CAN COME IN. 1242 01:06:57,043 --> 01:06:58,311 WE HAVE A DIFFERENT TECHNOLOGY 1243 01:06:58,311 --> 01:07:01,581 WHICH IS HOW DO I FIND A 1244 01:07:01,581 --> 01:07:06,553 SPECIFIC PROMOTER? 1245 01:07:06,553 --> 01:07:07,921 IT'S BASED ON SELF-CLEAVING 1246 01:07:07,921 --> 01:07:09,155 RNAs. 1247 01:07:09,155 --> 01:07:12,926 IF WE USE THAT CHEMISTRY TO FIND 1248 01:07:12,926 --> 01:07:15,262 THE RIGHT PROMOTERS WE MARRY 1249 01:07:15,262 --> 01:07:19,933 THEM AND ARE FURTHER LONG IN 1250 01:07:19,933 --> 01:07:29,709 ADVANCING THE THERAPY. 1251 01:07:29,709 --> 01:07:33,113 WHAT THAT IS AND WITH A COMPANY 1252 01:07:33,113 --> 01:07:37,984 IN CALIFORNIA CALLED 1253 01:07:37,984 --> 01:07:40,453 CIRCULARARIS, PROMOTERS GET 1254 01:07:40,453 --> 01:07:43,790 INCORPORATED INTO THE CIRCULAR 1255 01:07:43,790 --> 01:07:46,059 RNAs AND YOU CAN ANALYZE THEM IN 1256 01:07:46,059 --> 01:07:49,195 THE CELL TYPE OF CHOICE AND DO A 1257 01:07:49,195 --> 01:07:50,230 BAR-CODED READ OUT TO SEE WHICH 1258 01:07:50,230 --> 01:07:55,302 ONES ARE THE WINNERS. 1259 01:07:55,302 --> 01:07:58,972 AND ONE SUCH EXPERIMENT IS 1260 01:07:58,972 --> 01:08:00,507 SUMMARIZED HERE. 1261 01:08:00,507 --> 01:08:03,209 WE WERE LOOKING FOR PROMOTER AND 1262 01:08:03,209 --> 01:08:05,211 ENHANCER ELEMENTS THAT WOULD 1263 01:08:05,211 --> 01:08:08,181 GIVE US PREFERENTIAL EXPRESSION 1264 01:08:08,181 --> 01:08:14,020 EITHER IN THE LIVER OR IN THE 1265 01:08:14,020 --> 01:08:19,959 LUNG AND THE GRAPH SHOWS LI 1266 01:08:19,959 --> 01:08:22,295 EXPRESSION IN BOTH TISSUES IN 1267 01:08:22,295 --> 01:08:24,464 GREEN GOING UP TO THE TOP IN 1268 01:08:24,464 --> 01:08:27,200 PURPLE, HIGH IN THE LUNG, LOW IN 1269 01:08:27,200 --> 01:08:29,736 THE LIVER OR INDEED REPRESSED IN 1270 01:08:29,736 --> 01:08:31,838 THE LIVER GOING FURTHER TO THE 1271 01:08:31,838 --> 01:08:33,573 LEFT IN THE BLUE AND THEN SOME 1272 01:08:33,573 --> 01:08:35,942 LIVER SPECIFIC REPRESSORS THAT 1273 01:08:35,942 --> 01:08:41,147 HAVE NO THE LUNG ON IN THE FAR 1274 01:08:41,147 --> 01:08:43,950 LEFT AND THE DIFFERENT COLORS 1275 01:08:43,950 --> 01:08:46,019 REPRESENT ACTUAL GENETIC 1276 01:08:46,019 --> 01:08:46,486 SEQUENCES. 1277 01:08:46,486 --> 01:08:51,224 SO THIS WAS A SCREEN OF 800,000 1278 01:08:51,224 --> 01:08:53,293 REGULATORY ELEMENTS THAT WERE 1279 01:08:53,293 --> 01:08:56,663 COBBLED TOGETHER BY A VARIETY OF 1280 01:08:56,663 --> 01:08:56,963 TECHNIQUES. 1281 01:08:56,963 --> 01:08:59,833 SO IT'S REALLY FINDING NEEDLES 1282 01:08:59,833 --> 01:09:02,302 IN A HAYSTACK AND THAT'S REALLY 1283 01:09:02,302 --> 01:09:03,203 ONE OF THE POWERS OF OUR 1284 01:09:03,203 --> 01:09:10,610 PLATFORM. 1285 01:09:10,610 --> 01:09:12,746 OKAY. 1286 01:09:12,746 --> 01:09:14,414 SO, THAT'S WHAT THE INTRO SLIDE 1287 01:09:14,414 --> 01:09:16,916 WAS FOR AND WANTED TO SAY ASOME 1288 01:09:16,916 --> 01:09:20,820 WORDS ABOUT LPMs AND DOING 1289 01:09:20,820 --> 01:09:21,988 CELL-FREE PHOTO SYNTHESIS AND 1290 01:09:21,988 --> 01:09:28,428 THE IDEA IS TO DO THINGS LIKE 1291 01:09:28,428 --> 01:09:31,931 DISTRIBUTED MANUFACTURING A 1292 01:09:31,931 --> 01:09:33,767 COUPLE PICTURES I DREW FROM PAST 1293 01:09:33,767 --> 01:09:36,903 DARPA PROGRAMS FROM THE FIELD OR 1294 01:09:36,903 --> 01:09:38,304 DISTRIBUTED MANUFACTURING OF 1295 01:09:38,304 --> 01:09:38,638 THERAPEUTICS. 1296 01:09:38,638 --> 01:09:41,207 WE HAVE THE BIO MOD AND PHARMACY 1297 01:09:41,207 --> 01:09:45,912 ON DEMAND IN THE MIDDLE AND AT 1298 01:09:45,912 --> 01:09:50,350 THE RIGHT FROM UMBC AND TIM 1299 01:09:50,350 --> 01:09:52,952 JAMISON AT M.I.T. 1300 01:09:52,952 --> 01:09:57,056 SO, GINKO'S TRYING TO, IF YOU 1301 01:09:57,056 --> 01:09:58,858 WILL, BRING THE NEXT GENERATION 1302 01:09:58,858 --> 01:10:02,729 HERE AND THE IDEA WITH THE RPM 1303 01:10:02,729 --> 01:10:04,531 PROGRAM I'M SURE YOU'LL HEAR 1304 01:10:04,531 --> 01:10:06,833 MORE FROM MIKE AND I DON'T WANT 1305 01:10:06,833 --> 01:10:10,637 TO STEAL HIS THUNDER BUT 1306 01:10:10,637 --> 01:10:11,571 BASICALLY MAKE THERAPEUTIC 1307 01:10:11,571 --> 01:10:13,973 PROGRAMS USING CELL-FREE AND 1308 01:10:13,973 --> 01:10:18,545 ENSURE YOU MAKE A VERY PURE AND 1309 01:10:18,545 --> 01:10:19,946 CORRECTLY HUMANLY GLYCOSYLATED 1310 01:10:19,946 --> 01:10:21,514 PROTEINS WHICH IS ACTUALLY QUITE 1311 01:10:21,514 --> 01:10:26,219 DIFFICULT. 1312 01:10:26,219 --> 01:10:27,921 SO GINKO'S LEADING THE EFFORT. 1313 01:10:27,921 --> 01:10:29,422 WE HAVE A WONDERFUL TEAM AND THE 1314 01:10:29,422 --> 01:10:31,925 KEY PLAYERS ARE PICTURED HERE 1315 01:10:31,925 --> 01:10:35,662 BUT I WANTED TO HIGHLIGHT OUR 1316 01:10:35,662 --> 01:10:37,263 COLLABORATORS AT IMPERIAL 1317 01:10:37,263 --> 01:10:39,199 COLLEGE LONDON AND THEN AT 1318 01:10:39,199 --> 01:10:41,701 NATURE'S TOOLBOX WHICH IS A 1319 01:10:41,701 --> 01:10:47,941 SMALL START OFF FROM LOS ALAMOS 1320 01:10:47,941 --> 01:10:48,808 LAB IN NEW MEXICO. 1321 01:10:48,808 --> 01:10:50,477 AND A SCHEMATIC ABOUT WHAT WE'RE 1322 01:10:50,477 --> 01:10:53,046 DOING WHICH INVOLVES AS YOU 1323 01:10:53,046 --> 01:10:55,748 MIGHT EXPECT, DISCOVERY, 1324 01:10:55,748 --> 01:10:58,485 OPTIMIZATION AND THEN 1325 01:10:58,485 --> 01:10:58,985 DEPLOYMENT. 1326 01:10:58,985 --> 01:11:00,086 IT'S DESIGN, BUILT TEST JUST 1327 01:11:00,086 --> 01:11:06,226 TAKEN TO THE NEXT STEP. 1328 01:11:06,226 --> 01:11:06,559 OKAY. 1329 01:11:06,559 --> 01:11:08,761 AN ACTUAL CASE STUDY. 1330 01:11:08,761 --> 01:11:12,799 SO WE'VE BEEN WORKING WITH A 1331 01:11:12,799 --> 01:11:17,303 COMPANY CALLED SYN LOGIC 1332 01:11:17,303 --> 01:11:19,472 BRINGING LIVING THERAPEUTICS TO 1333 01:11:19,472 --> 01:11:22,909 THE CLINIC AND HOPEFULLY SOON 1334 01:11:22,909 --> 01:11:23,142 BEYOND. 1335 01:11:23,142 --> 01:11:24,944 SO OUR COLLABORATION WITH THEM 1336 01:11:24,944 --> 01:11:27,547 DATES BACK NOW I THINK ABOUT SIX 1337 01:11:27,547 --> 01:11:27,881 YEARS. 1338 01:11:27,881 --> 01:11:28,781 IT COVERS SOMETHING LIKE 10 1339 01:11:28,781 --> 01:11:29,349 PROGRAMS AND THIS IS ONE OF 1340 01:11:29,349 --> 01:11:37,690 THOSE. 1341 01:11:37,690 --> 01:11:39,926 THEY WANTED TO COME UP WITH A 1342 01:11:39,926 --> 01:11:45,198 LIVING ORGANISM, AN E. COLI YOU 1343 01:11:45,198 --> 01:11:51,938 EAT TREATING THIS RARE DISEASE 1344 01:11:51,938 --> 01:12:02,482 CALLED HOMOCYSTINURIA AND CAN WE 1345 01:12:10,957 --> 01:12:13,560 MAKE WHAT IS FURTHER ENGINEERED 1346 01:12:13,560 --> 01:12:15,295 BY PUTTING THE RIGHT METABOLISM 1347 01:12:15,295 --> 01:12:21,200 IN IT SO WHEN YOU EAT THIS IT 1348 01:12:21,200 --> 01:12:26,139 WILL CHEW UP THE METHIONINE AND 1349 01:12:26,139 --> 01:12:28,942 THE DATA GRAPHS SHOW THE 1350 01:12:28,942 --> 01:12:31,911 OPTIMIZATION ATOP OF ONE OF THE 1351 01:12:31,911 --> 01:12:42,422 ENZYMES IN THE DESIGN PATHWAY. 1352 01:12:50,797 --> 01:12:51,931 OTHERS HAT HIGHER ACTIVITY BUT 1353 01:12:51,931 --> 01:12:57,503 WHEN PUT IT IN THE CONTEXT OF 1354 01:12:57,503 --> 01:13:06,479 THE FULL ORGANISM AND MAYBE IT'S 1355 01:13:06,479 --> 01:13:11,651 NOT THE BEST CLINICAL CANDIDATE 1356 01:13:11,651 --> 01:13:19,692 AND LOTS OF VARIANTS AND COPY 1357 01:13:19,692 --> 01:13:23,730 NUMBER TO OPTIMIZE THE OVER ALL 1358 01:13:23,730 --> 01:13:25,498 METABOLISM AND IT'S SHOWN AT THE 1359 01:13:25,498 --> 01:13:26,265 BOTTOM GRAPH. 1360 01:13:26,265 --> 01:13:34,741 THIS IS THE DEPLETION OF 1361 01:13:34,741 --> 01:13:41,547 METHIONINE AND CYSTINE AND THE 1362 01:13:41,547 --> 01:13:43,483 GRAPH AT THE BOTTOM KIND OF RED 1363 01:13:43,483 --> 01:13:47,320 IS THE DRUG COMPARED TO THE 1364 01:13:47,320 --> 01:13:50,590 CONTROLS OR THE EMPTY E. COLI 1365 01:13:50,590 --> 01:13:50,823 VECTOR. 1366 01:13:50,823 --> 01:13:55,962 THE EMPTY E. COLI. 1367 01:13:55,962 --> 01:13:59,932 THIS DID THE JOB SO IT 1368 01:13:59,932 --> 01:14:08,474 PROGRESSED. 1369 01:14:08,474 --> 01:14:19,185 AND THIS IS NOW CALLED SYNB1353 1370 01:14:19,185 --> 01:14:22,422 AND FINISHED PHASE I AND GOING 1371 01:14:22,422 --> 01:14:23,389 TO PHASE II. 1372 01:14:23,389 --> 01:14:25,425 THIS IS MY WRAP-UP, PRODUCTION 1373 01:14:25,425 --> 01:14:25,725 AND SCALE. 1374 01:14:25,725 --> 01:14:27,126 I MENTIONED OUR ABILITY TO 1375 01:14:27,126 --> 01:14:29,095 SCREEN THINGS LIKE PROMOTERS AND 1376 01:14:29,095 --> 01:14:36,969 FIND ONES THAT WORK WELL AND WE 1377 01:14:36,969 --> 01:14:40,707 PRODUCED A WORKFORCE FOR 1378 01:14:40,707 --> 01:14:42,508 INDUSTRIAL BIO TECHNOLOGY. 1379 01:14:42,508 --> 01:14:46,646 IT IS A SHETLAND PONY IN THE 1380 01:14:46,646 --> 01:14:47,714 PHARMA SPACE BUT IT'S GROWING OR 1381 01:14:47,714 --> 01:14:49,649 MAYBE WILL GROW ESPECIALLY IF WE 1382 01:14:49,649 --> 01:14:55,354 CAN ENGINEER IT TO MAKE HUMAN 1383 01:14:55,354 --> 01:14:56,055 GLYCANS EFFECTIVELY. 1384 01:14:56,055 --> 01:15:01,160 WE HAVE A PICIHA PRODUCING 1385 01:15:01,160 --> 01:15:01,994 WITHOUT METHANOL PRODUCING WHICH 1386 01:15:01,994 --> 01:15:05,865 IS STANDARD IN THE ACADEMIC 1387 01:15:05,865 --> 01:15:06,365 SPACE. 1388 01:15:06,365 --> 01:15:07,967 A LITTLE BIT IN THE INDUSTRIAL 1389 01:15:07,967 --> 01:15:09,235 SPACE BUT PEOPLE HATE IT BECAUSE 1390 01:15:09,235 --> 01:15:11,938 YOU DON'T WANT TO WORK WITH 50 1391 01:15:11,938 --> 01:15:13,706 LITER FERMENTERS YOU HAVE TO 1392 01:15:13,706 --> 01:15:14,440 PUMP METHANOL INTO. 1393 01:15:14,440 --> 01:15:20,947 WE HAVE A METHANOL-FREE SYSTEM 1394 01:15:20,947 --> 01:15:23,416 THAT WORKS WAY BETTER THAN THE 1395 01:15:23,416 --> 01:15:27,253 METHANOL INDUCED SYSTEM WHICH 1396 01:15:27,253 --> 01:15:28,421 HAS BEEN AMAZING. 1397 01:15:28,421 --> 01:15:35,128 THE EXAMPLE AT THE BOTTOM IS A 1398 01:15:35,128 --> 01:15:37,830 FLUORESCENT PROTEIN AND WE HAVE 1399 01:15:37,830 --> 01:15:40,867 AN ENTIRE FERMENTATION GROUP AND 1400 01:15:40,867 --> 01:15:43,536 THE AMBER 250s OVER 300 UNITS. 1401 01:15:43,536 --> 01:15:47,940 WE'RE USING THESE THINGS IN ALL 1402 01:15:47,940 --> 01:15:53,813 KINDS OF PROGRAMS TO OPTIMIZE 1403 01:15:53,813 --> 01:15:55,882 THE STRANDZ -- 1404 01:15:57,850 --> 01:15:59,552 THE STRAINS THAT COME IN AND THE 1405 01:15:59,552 --> 01:16:00,853 PREDICTION ON THE LEFT WHICH IS 1406 01:16:00,853 --> 01:16:03,189 HOW DO I NEED TO RUN THE 1407 01:16:03,189 --> 01:16:04,857 FERMENTER AS DETERMINED IN THESE 1408 01:16:04,857 --> 01:16:15,334 LITTLE THINGS ONLY THIS BIG. 1409 01:16:18,437 --> 01:16:20,673 THE AMBER PREDICTION WAS IN THE 1410 01:16:20,673 --> 01:16:24,877 LITTLE BOX AT THE FAR RIGHT, THE 1411 01:16:24,877 --> 01:16:25,144 UPPER BOX. 1412 01:16:25,144 --> 01:16:28,748 THE CUSTOMER WANTED TO DO A 1413 01:16:28,748 --> 01:16:29,882 PILOT SCALE BECAUSE NATURALLY 1414 01:16:29,882 --> 01:16:31,317 THEY DIDN'T BELIEVE US. 1415 01:16:31,317 --> 01:16:35,154 THEY RAN THE PILOT EXPERIMENT. 1416 01:16:35,154 --> 01:16:37,456 THAT'S THE BLUE LINE THEN RAN 1417 01:16:37,456 --> 01:16:38,624 THE COMMERCIAL SCALE AND TRACKED 1418 01:16:38,624 --> 01:16:39,992 TO PILOT AND GOT TO WHERE WE 1419 01:16:39,992 --> 01:16:42,028 SAID IT WOULD GET TO AND CAME 1420 01:16:42,028 --> 01:16:43,596 BACK AND SAID THIS IS TOO HARD 1421 01:16:43,596 --> 01:16:44,897 TO RUN IN A PLANT. 1422 01:16:44,897 --> 01:16:46,999 WE CAN'T TURN THE VALVES THAT 1423 01:16:46,999 --> 01:16:47,733 FAST, IF YOU WILL. 1424 01:16:47,733 --> 01:16:51,237 SO CAN YOU COME UP WITH A 1425 01:16:51,237 --> 01:16:52,839 SIMPLER PROCESS. 1426 01:16:52,839 --> 01:16:57,176 WE RE-ENGINEERED THE PROCESS AND 1427 01:16:57,176 --> 01:16:58,044 THAT'S THE LOWER PURPLE BOX AT 1428 01:16:58,044 --> 01:17:04,250 THE TOP RIGHT. 1429 01:17:04,250 --> 01:17:05,918 SIMPLER PROCESS NOW UP AND 1430 01:17:05,918 --> 01:17:07,453 RUNNING. 1431 01:17:07,453 --> 01:17:09,722 WE HAVE A PARTNER FACILITY 1432 01:17:09,722 --> 01:17:14,727 COMPANY CALLS FERMIC BASED IN 1433 01:17:14,727 --> 01:17:17,530 MEXICO CITY AND MANY PARTNERS 1434 01:17:17,530 --> 01:17:19,932 HAVE PRODUCING WITH FERMIC AND 1435 01:17:19,932 --> 01:17:23,102 THESE THE TANKS THAT HOLD THE 1436 01:17:23,102 --> 01:17:25,037 CASTOR OIL THAT GOES IN THE 1437 01:17:25,037 --> 01:17:26,539 FERMENTATION AND THEY'RE 50,000 1438 01:17:26,539 --> 01:17:26,839 LITERS. 1439 01:17:26,839 --> 01:17:28,341 IT GIVES A SENSE OF HOW BIG IT 1440 01:17:28,341 --> 01:17:28,641 IS. 1441 01:17:28,641 --> 01:17:32,078 IT'S PRETTY BIG. 1442 01:17:32,078 --> 01:17:35,581 WE USED THIS SYSTEM WITH OUR 1443 01:17:35,581 --> 01:17:38,217 SPIN-OFF COMPANY MOTIF IN THE 1444 01:17:38,217 --> 01:17:39,819 ENGINEERED PROTEINS FOR FOOD 1445 01:17:39,819 --> 01:17:40,219 SPACE. 1446 01:17:40,219 --> 01:17:43,089 AND THEY WANTED A PROTEIN THEY 1447 01:17:43,089 --> 01:17:44,257 COULD PUT INTO BURGERS. 1448 01:17:44,257 --> 01:17:47,059 THEY WANTED SOMETHING TO MAKE 1449 01:17:47,059 --> 01:17:51,497 THE BURGERS RED AND TASTE GOOD. 1450 01:17:51,497 --> 01:17:54,233 WE STARTED AT THE BOTTOM LEFT 1451 01:17:54,233 --> 01:17:57,069 AND DID A HUGE SCREEN, THOUSANDS 1452 01:17:57,069 --> 01:18:03,142 AND THOUSANDS OF GLOBIN 1453 01:18:03,142 --> 01:18:05,177 CONTAINING MOLECULES, MYOGLOBIN 1454 01:18:05,177 --> 01:18:06,913 AND OTHERS AND WE SCREENED AND 1455 01:18:06,913 --> 01:18:08,614 OPTIMIZED AND YADDA, YADDA, IN 1456 01:18:08,614 --> 01:18:12,852 THE END WE DELIVERED THE WINNER. 1457 01:18:12,852 --> 01:18:19,926 THE IRONIC THING IS THE WINNER 1458 01:18:19,926 --> 01:18:28,668 IS MYOGLOBIN AND CHEETAH WAS THE 1459 01:18:28,668 --> 01:18:31,170 RUNNER UP SO MAYBE SOME DAY 1460 01:18:31,170 --> 01:18:32,438 THEY'LL DO CHEETAH BURGERS. 1461 01:18:32,438 --> 01:18:35,174 THEY BROUGHT THIS TO MARK AND 1462 01:18:35,174 --> 01:18:36,008 THIS IS GOING TO BE COMING UP 1463 01:18:36,008 --> 01:18:38,778 SOON AND HAPPY TO TAKE ANY 1464 01:18:38,778 --> 01:18:39,278 QUESTIONS YOU HAVE. 1465 01:18:39,278 --> 01:18:49,455 THANK YOU. 1466 01:18:57,797 --> 01:19:01,801 >> I'M CURIOUS IF YOUR SERVICES 1467 01:19:01,801 --> 01:19:03,736 CAN EXTEND TO SMALL-SCALE 1468 01:19:03,736 --> 01:19:05,805 SPINOFFS TO ACADEMIC LABS JUST 1469 01:19:05,805 --> 01:19:06,672 GETTING STARTED IF THERE'S A 1470 01:19:06,672 --> 01:19:10,710 PILOT PROCESS THAT CAN BE RUN 1471 01:19:10,710 --> 01:19:15,281 FOR THAT TYPE OF LEVEL OR IF 1472 01:19:15,281 --> 01:19:19,251 GINKO'S JUST TOO BIG ESSENTIALLY 1473 01:19:19,251 --> 01:19:21,620 TO THAT LEVEL OF LABORATORY OR 1474 01:19:21,620 --> 01:19:22,755 ORGANIZATION CAN AFFORD? 1475 01:19:22,755 --> 01:19:23,956 >> GOOD QUESTION. 1476 01:19:23,956 --> 01:19:27,793 THANK YOU. 1477 01:19:27,793 --> 01:19:29,362 SO IF YOU CAST YOUR MIND BACK TO 1478 01:19:29,362 --> 01:19:31,063 THE PICTURE WITH ALL THE LOGOS, 1479 01:19:31,063 --> 01:19:33,165 I WOULD SAY ABOUT HALF THE 1480 01:19:33,165 --> 01:19:34,800 COMPANIES MAYBE TWO-THIRDS THAT 1481 01:19:34,800 --> 01:19:35,935 WE'RE WORKING WITH ARE VERY 1482 01:19:35,935 --> 01:19:36,535 SMALL. 1483 01:19:36,535 --> 01:19:45,277 SO THEY'RE START UPS. 1484 01:19:45,277 --> 01:19:47,380 WE'RE HAPPY TO ENTERTAIN 1485 01:19:47,380 --> 01:19:48,681 POSSIBILITIES AND TALK ABOUT IT. 1486 01:19:48,681 --> 01:19:51,951 BOTH FROM THE POINT OF VIEW OF 1487 01:19:51,951 --> 01:19:53,719 CAN WE WORK TOGETHER IN SOME 1488 01:19:53,719 --> 01:19:55,955 SORT OF COMMERCIAL SENSE TO 1489 01:19:55,955 --> 01:19:58,090 BRING THE SMALL COMPANY TO ITS 1490 01:19:58,090 --> 01:19:59,492 INFLECTION POINT, WHATEVER THE 1491 01:19:59,492 --> 01:20:01,460 NEXT VALUE INFLECTION POINT IS 1492 01:20:01,460 --> 01:20:04,864 BUT ALSO TO PARTNER ON 1493 01:20:04,864 --> 01:20:05,731 CUTTING-EDGE RESEARCH. 1494 01:20:05,731 --> 01:20:11,737 SO GO AFTER GOVERNMENT FUNDING 1495 01:20:11,737 --> 01:20:15,107 THAT WILL LED US TOGETHER 1496 01:20:15,107 --> 01:20:16,575 SOMETHING BIGGER THAN WE CAN DO 1497 01:20:16,575 --> 01:20:17,443 ALONE. 1498 01:20:17,443 --> 01:20:17,743 ABSOLUTELY. 1499 01:20:17,743 --> 01:20:20,146 >> THAT'S VERY GOOD NEWS. 1500 01:20:20,146 --> 01:20:25,918 THANK YOU. 1501 01:20:25,918 --> 01:20:27,520 >> I WONDERED ABOUT THE SCALE OF 1502 01:20:27,520 --> 01:20:31,023 AUTOMATION YOU GUYS ARE WORKING 1503 01:20:31,023 --> 01:20:31,357 WITH. 1504 01:20:31,357 --> 01:20:33,259 SCREENING FOR THE DIFFERENT 1505 01:20:33,259 --> 01:20:33,959 ITERATIONS BUT HOW MUCH BENCH 1506 01:20:33,959 --> 01:20:39,198 WORK IS ACTUALLY GOING ON 1507 01:20:39,198 --> 01:20:43,903 BYPRODUCT THE SCENES, IS IT PLUG 1508 01:20:43,903 --> 01:20:44,437 AND PLAY. 1509 01:20:44,437 --> 01:20:46,705 >> IDEALLY THE ROBOTS WOULD BE 1510 01:20:46,705 --> 01:20:49,975 DOING ALL THE WORK BUT AS YOU 1511 01:20:49,975 --> 01:20:55,381 WALK THROUGH AND TOUR GINKO LABS 1512 01:20:55,381 --> 01:20:58,818 YOU'LL SEE WE HAVE ABOUT 1200 1513 01:20:58,818 --> 01:21:00,753 PEOPLE IN THE LAB. 1514 01:21:00,753 --> 01:21:01,053 SCIENTISTS. 1515 01:21:01,053 --> 01:21:10,596 IT'S ABOUT 600, I GUESS. 1516 01:21:10,596 --> 01:21:14,700 THERE'S AN ENTIRE SOFTWARE STACK 1517 01:21:14,700 --> 01:21:18,237 THAT RUNS THE WHOLE THING FROM 1518 01:21:18,237 --> 01:21:19,939 DESIGN OF EXPERIMENT TO 1519 01:21:19,939 --> 01:21:24,543 SCHEDULING ON THE ROBOTS TO 1520 01:21:24,543 --> 01:21:26,245 RUNNING OF EXPERIMENT, BANKING 1521 01:21:26,245 --> 01:21:31,383 AND ANALYZING AND LEARNING FROM 1522 01:21:31,383 --> 01:21:32,952 THE DATA. 1523 01:21:32,952 --> 01:21:33,919 THAT'S WHY WE HAVE 120 PEOPLE 1524 01:21:33,919 --> 01:21:35,921 DOING THAT BUT AS YOU WALK 1525 01:21:35,921 --> 01:21:38,624 AROUND YOU'LL SEE PEOPLE AND IT 1526 01:21:38,624 --> 01:21:39,925 DEPENDS ON THE PROJECT. 1527 01:21:39,925 --> 01:21:43,596 SOMETHING LIKE THE DARPA RPM IS 1528 01:21:43,596 --> 01:21:47,933 A GOOD EXAMPLE. 1529 01:21:47,933 --> 01:21:49,702 IT'S CUTTING-EDGE 1530 01:21:49,702 --> 01:21:51,203 EXPERIMENTATION AND FOOLING 1531 01:21:51,203 --> 01:21:52,538 AROUND AND YOU'LL SEE STUFF IN 1532 01:21:52,538 --> 01:21:53,639 THE LABORATORY WITH PEOPLE AND 1533 01:21:53,639 --> 01:21:59,211 IT'S LIKE OKAY, NOW I HAVE A 1534 01:21:59,211 --> 01:22:09,755 LIBRARY OF 3,000 GLYCOTRANSFER 1535 01:22:15,327 --> 01:22:20,299 A 1536 01:22:20,299 --> 01:22:20,933 GLYCOTRANSFERASS AND HAVE TO GET 1537 01:22:20,933 --> 01:22:21,567 PUSH BUTTON AND SOMETIMES YOU'LL 1538 01:22:21,567 --> 01:22:22,201 SEE PEOPLE LOADING PLATES BUT I 1539 01:22:22,201 --> 01:22:22,835 DON'T KNOW HOW MANY ROBOTS TOTAL 1540 01:22:22,835 --> 01:22:23,836 NOW. 1541 01:22:23,836 --> 01:22:26,338 THE NUMBER 300 PLUS WAS BOUNCING 1542 01:22:26,338 --> 01:22:31,310 AROUND AND WE BROUGHT IN NEW 1543 01:22:31,310 --> 01:22:34,747 AUTO MATION THE RECONFIGUREABLE 1544 01:22:34,747 --> 01:22:36,315 AUTOMATED CARTS WHERE EACH 1545 01:22:36,315 --> 01:22:39,285 MACHINE THAT DOES A UNIT 1546 01:22:39,285 --> 01:22:43,455 OPERATION LIKE A PLATE SEALING, 1547 01:22:43,455 --> 01:22:44,890 CENTRIFUGATION ARE INSIDE OF BOX 1548 01:22:44,890 --> 01:22:47,660 ON WHEELS AND YOU CAN LITERALLY 1549 01:22:47,660 --> 01:22:51,263 DRIVE THEM AROUND AND PLUG THEM 1550 01:22:51,263 --> 01:22:52,531 INTO A RAILROAD TRACK THAT 1551 01:22:52,531 --> 01:22:54,800 DRIVES THE PLATES AROUND. 1552 01:22:54,800 --> 01:23:01,440 IF YOU WANT A NEW WORK FLOW YOU 1553 01:23:01,440 --> 01:23:04,009 LINE UP THE PARTS IN ORDER AND 1554 01:23:04,009 --> 01:23:05,678 YOU'RE UP AND RUNNING. 1555 01:23:05,678 --> 01:23:07,279 WE ARE DEPLOYING MORE AND MORE 1556 01:23:07,279 --> 01:23:07,713 OF THOSE. 1557 01:23:07,713 --> 01:23:12,651 >> VERY COOL. 1558 01:23:12,651 --> 01:23:16,322 THANK YOU. 1559 01:23:16,322 --> 01:23:16,922 >> THANK YOU. 1560 01:23:16,922 --> 01:23:18,857 ONE QUESTION I HAVE STRUCK BY 1561 01:23:18,857 --> 01:23:22,928 THE NUMBER OF PROJECTS, ENZYMES 1562 01:23:22,928 --> 01:23:25,097 EXPRESSED, EASIES AS YOU FLASH 1563 01:23:25,097 --> 01:23:26,832 UP BILLIONS OF MOLECULES AND 1564 01:23:26,832 --> 01:23:31,904 WONDERING HOW THAT CONTRIBUTE TO 1565 01:23:31,904 --> 01:23:36,742 A.I., CURIOUS, ARE THERE IS 1566 01:23:36,742 --> 01:23:38,811 THERE A FRACTION OF MAKING THAT 1567 01:23:38,811 --> 01:23:40,879 OPEN SOURCE AND RECOGNIZING SOME 1568 01:23:40,879 --> 01:23:42,815 IS INTERNAL AND MUCH FUNDED BY 1569 01:23:42,815 --> 01:23:43,949 GOVERNMENT GRANTS AND TRYING TO 1570 01:23:43,949 --> 01:23:47,419 MOVE IN A NEW WORLD OF A.I. 1571 01:23:47,419 --> 01:23:48,254 WHERE WE CAN LEVERAGE THE 1572 01:23:48,254 --> 01:23:49,655 INFORMATION AND WONDERING WHAT 1573 01:23:49,655 --> 01:23:50,789 THE DISCUSSIONS ARE LIKE INSIDE 1574 01:23:50,789 --> 01:23:51,290 GINKO. 1575 01:23:51,290 --> 01:23:59,164 >> GREAT QUESTION. 1576 01:23:59,164 --> 01:24:01,066 THE WORK WE'RE DOING LEVERAGING 1577 01:24:01,066 --> 01:24:02,434 THE GOOGLE RESOURCES IS BRAND 1578 01:24:02,434 --> 01:24:02,601 NEW. 1579 01:24:02,601 --> 01:24:08,173 WHAT WE'VE BEEN TALK ABOUT IN IN 1580 01:24:08,173 --> 01:24:10,976 TERM 1581 01:24:10,976 --> 01:24:14,146 TERMLY SO NOW PROMISES YET BUT 1582 01:24:14,146 --> 01:24:16,749 WE'LL BE DEVELOPING A VOICE OF 1583 01:24:16,749 --> 01:24:17,916 FOUNDATION MODELS AND 1584 01:24:17,916 --> 01:24:19,585 TASK-SPECIFIC MODELS AND THAT 1585 01:24:19,585 --> 01:24:26,992 OUR INTENTION IS TO BE RELEASING 1586 01:24:26,992 --> 01:24:31,964 SOME FOR PUBLIC USE ON THE 1587 01:24:31,964 --> 01:24:37,903 GOOGLE SERVERS. 1588 01:24:37,903 --> 01:24:39,305 >> I RECOGNIZE A LOT OF IS 1589 01:24:39,305 --> 01:24:39,738 PROPRIETARY. 1590 01:24:39,738 --> 01:24:42,908 >> AS FOR THE DATA ITSELF, I 1591 01:24:42,908 --> 01:24:46,812 DON'T THINK SO. 1592 01:24:46,812 --> 01:24:50,816 IF YOU THINK ABOUT SORT OF WHAT 1593 01:24:50,816 --> 01:24:52,584 MAKES A.I. WORK IT'S THE DATA. 1594 01:24:52,584 --> 01:24:54,920 IT'S ALL ABOUT THE DATA. 1595 01:24:54,920 --> 01:24:55,954 THAT'S FRANKLY A HUGE 1596 01:24:55,954 --> 01:25:02,061 COMPETITIVE ADVANTAGE FOR GINKO. 1597 01:25:02,061 --> 01:25:04,163 THE MODELS THEMSELVES I THINK WE 1598 01:25:04,163 --> 01:25:05,464 WILL. 1599 01:25:05,464 --> 01:25:06,598 IF YOU THINK HAVING A TRAINED 1600 01:25:06,598 --> 01:25:08,033 MODEL IT'S LIKE YOU DON'T NEED 1601 01:25:08,033 --> 01:25:15,474 THE DATA ANY MORE. 1602 01:25:15,474 --> 01:25:19,044 I WANT TO USE THE NEW MODEL WITH 1603 01:25:19,044 --> 01:25:22,214 GOOGLE'S HELP TO DESIGN MY NEW 1604 01:25:22,214 --> 01:25:23,949 PROTEIN AND YOU JUST NEED THE 1605 01:25:23,949 --> 01:25:30,622 MODEL. 1606 01:25:30,622 --> 01:25:39,365 >> THANK YOU. 1607 01:25:39,365 --> 01:25:39,598 J OKAY. 1608 01:25:39,598 --> 01:25:42,334 WE'RE GOING TO WRAP UP THIS 1609 01:25:42,334 --> 01:25:45,304 MORNING'S TALKS WITH THE 1610 01:25:45,304 --> 01:25:46,972 EDUCATIONAL OPPORTUNITIES 1611 01:25:46,972 --> 01:25:50,976 AVAILABLE FROM THE FOUNDATION 1612 01:25:50,976 --> 01:25:54,580 FOR THE ADVANCED EDUCATION IN 1613 01:25:54,580 --> 01:26:05,090 SCIENCES FROM DR. MINDY MARIS. 1614 01:26:08,427 --> 01:26:09,294 >> GOOD MORNING, EVERYBODY. 1615 01:26:09,294 --> 01:26:11,630 I KNOW I'M PROBABLY THE ONLY 1616 01:26:11,630 --> 01:26:13,265 THING STANDING BETWEEN YOU AND 1617 01:26:13,265 --> 01:26:15,134 LUNCH SO I WILL TRY TO KEEP 1618 01:26:15,134 --> 01:26:15,834 THESE REMARKS VERY BRIEF. 1619 01:26:15,834 --> 01:26:18,704 AS ONE OF THE SPONSORS OF THIS 1620 01:26:18,704 --> 01:26:19,938 CONFERENCE, WE'RE VERY PLEASED 1621 01:26:19,938 --> 01:26:21,907 AT THE FOUNDATION FOR ADVANCE 1622 01:26:21,907 --> 01:26:22,708 EDUCATION IN THE SCIENCE TO HELP 1623 01:26:22,708 --> 01:26:24,743 SPONSOR THIS CONFERENCE AND I 1624 01:26:24,743 --> 01:26:25,444 REALLY APPRECIATE THE 1625 01:26:25,444 --> 01:26:26,678 OPPORTUNITY TO TELL YOU A LITTLE 1626 01:26:26,678 --> 01:26:28,147 BIT ABOUT WHO WE ARE AND WHAT WE 1627 01:26:28,147 --> 01:26:31,417 OFFER THAT MIGHT BE HELPFUL TO 1628 01:26:31,417 --> 01:26:33,318 THE ADVANCEMENT OF YOUR CAREERS 1629 01:26:33,318 --> 01:26:35,954 OR OF THE TRAINEES YOU HAVE IN 1630 01:26:35,954 --> 01:26:39,858 YOUR LABS. 1631 01:26:39,858 --> 01:26:42,761 SO FOR THOSE WHO MAY NOT KNOW 1632 01:26:42,761 --> 01:26:43,529 ABOUT OUR ORGANIZATION. 1633 01:26:43,529 --> 01:26:45,564 THE FOUNDATION FOR ADVANCED 1634 01:26:45,564 --> 01:26:46,799 EDUCATION IN THE SCIENCES WAS 1635 01:26:46,799 --> 01:26:48,634 FOUNDED OVER 60 YEARS AGO BY A 1636 01:26:48,634 --> 01:26:51,136 GROUP OF NIH SCIENTISTS WHO 1637 01:26:51,136 --> 01:26:53,372 ESSENTIALLY WANTED TO CREATE A 1638 01:26:53,372 --> 01:26:54,106 UNIVERSITY-LIKE ENTITY. 1639 01:26:54,106 --> 01:26:54,873 BASICALLY THEY WANTED 1640 01:26:54,873 --> 01:26:55,941 OPPORTUNITIES TO TEACH AND TO 1641 01:26:55,941 --> 01:26:57,810 LEARN. 1642 01:26:57,810 --> 01:27:00,946 AND SO WE ARE AN INDEPENDENT 1643 01:27:00,946 --> 01:27:02,481 NON-PROFIT ORGANIZATION LOCATED 1644 01:27:02,481 --> 01:27:06,518 ON THE BETHESDA CAMPUS ON THE 1645 01:27:06,518 --> 01:27:08,187 NIH IN BUILDING 10 IN THE 1646 01:27:08,187 --> 01:27:09,822 CLINICAL CENTER SO FEEL FREE TO 1647 01:27:09,822 --> 01:27:13,926 STOP BY AND SAY HI AND WE WORK 1648 01:27:13,926 --> 01:27:17,396 WITH THE NIH IN SEEKING AND 1649 01:27:17,396 --> 01:27:19,164 APPLYING FUNDAMENTAL KNOWLEDGE 1650 01:27:19,164 --> 01:27:20,466 ON THE BIOMEDICAL SCIENCE. 1651 01:27:20,466 --> 01:27:22,501 WE OFFER CREDIT-INITIATIVES AND 1652 01:27:22,501 --> 01:27:23,802 NON-CREDIT INITIATIVES IN 1653 01:27:23,802 --> 01:27:24,937 SUBJECT AREAS THAT COMPLIMENT 1654 01:27:24,937 --> 01:27:26,638 THE RESEARCH AND CAREER 1655 01:27:26,638 --> 01:27:28,106 DEVELOPMENT OF THE NIH COMMUNITY 1656 01:27:28,106 --> 01:27:29,274 AS WELL AS THE BROADER BIO 1657 01:27:29,274 --> 01:27:29,875 MEDICAL COMMUNITY. 1658 01:27:29,875 --> 01:27:35,914 AND SO THAT'S PROBABLY ONE KEY 1659 01:27:35,914 --> 01:27:43,288 POINT HOPEFULLY OUR PROGRAMS ARE 1660 01:27:43,288 --> 01:27:45,290 LOCATED TO THOSE ONLINE AND 1661 01:27:45,290 --> 01:27:47,459 THEY'RE HIGHLY ACCESSIBLE AND 1662 01:27:47,459 --> 01:27:48,660 FLEXIBLE NO MATTER WHERE YOU'RE 1663 01:27:48,660 --> 01:27:50,596 LOCATED OR WHAT TIME ZONE YOU'RE 1664 01:27:50,596 --> 01:27:50,963 IN. 1665 01:27:50,963 --> 01:27:52,898 AND SO AS I MENTIONED BRIEFLY ON 1666 01:27:52,898 --> 01:27:55,000 THE PREVIOUS SLIDE OUR ACADEMIC 1667 01:27:55,000 --> 01:27:57,069 INITIATIVES CAN BE BROADLY 1668 01:27:57,069 --> 01:27:59,771 DIVIDED INTO TWO CATEGORIES. 1669 01:27:59,771 --> 01:28:01,573 OUR NON-CREDIT INITIATIVES WE 1670 01:28:01,573 --> 01:28:03,308 REFER TO AS WORKSHOPS AND 1671 01:28:03,308 --> 01:28:05,711 ACADEMIC COURSES WHICH ARE 1672 01:28:05,711 --> 01:28:06,512 CREDIT-BEARING. 1673 01:28:06,512 --> 01:28:07,913 I'LL TELL YOU MORE ABOUT THE 1674 01:28:07,913 --> 01:28:09,414 FORMAT AND BENEFITS AND WHO 1675 01:28:09,414 --> 01:28:11,116 THESE ARE BEST SUITED FOR ON THE 1676 01:28:11,116 --> 01:28:12,217 FOLLOWING SLIDE BUT ESSENTIALLY 1677 01:28:12,217 --> 01:28:15,320 MOST OF OUR WORKSHOPS ARE 1678 01:28:15,320 --> 01:28:17,823 OFFERED IN A LIVE SYNCHRONOUS 1679 01:28:17,823 --> 01:28:19,925 FORMAT THOUGH FULLY ONLINE AND 1680 01:28:19,925 --> 01:28:21,226 THESE TEND TO BE HELD EITHER 1681 01:28:21,226 --> 01:28:23,662 OVER TWO TO FIVE CONSECUTIVE 1682 01:28:23,662 --> 01:28:25,297 DAYS OR SOMETIMES ONE TO TWO 1683 01:28:25,297 --> 01:28:26,498 SESSIONS OVER SEVERAL WEEKS. 1684 01:28:26,498 --> 01:28:29,067 OUR ACADEMIC COURSES THEY FOLLOW 1685 01:28:29,067 --> 01:28:31,270 AN ACADEMIC CALENDAR I'M SURE 1686 01:28:31,270 --> 01:28:32,638 ALL ARE FAMILIAR WITH FROM YOUR 1687 01:28:32,638 --> 01:28:33,739 TIME IN SCHOOL. 1688 01:28:33,739 --> 01:28:35,274 TYPICALLY SEVEN WEEKS LONG AND 1689 01:28:35,274 --> 01:28:36,608 TWO CREDITS. 1690 01:28:36,608 --> 01:28:37,976 WE'RE A NON-DEGREE GRANTING 1691 01:28:37,976 --> 01:28:39,311 ORGANIZATION BECAUSE THE 1692 01:28:39,311 --> 01:28:41,947 MAJORITY OF OUR LEARNERS ARE 1693 01:28:41,947 --> 01:28:43,749 ALREADY HIGHLY DEGREED. 1694 01:28:43,749 --> 01:28:45,317 HAVE YOU THE TERMINAL DEGREE IN 1695 01:28:45,317 --> 01:28:47,219 YOUR FIELD AND A WHOLE LOT OF 1696 01:28:47,219 --> 01:28:48,387 SCHOOLING BEHIND YOU. 1697 01:28:48,387 --> 01:28:53,125 WHAT WE OFFER ARE 1698 01:28:53,125 --> 01:28:54,026 MICROCREDE 1699 01:28:54,026 --> 01:28:54,426 MICROCREDENTIALS. 1700 01:28:54,426 --> 01:28:55,627 CAN DEMONSTRATE TO THE OUTSIDE 1701 01:28:55,627 --> 01:28:57,696 WORLD YOU GAINED A NEW BODY OF 1702 01:28:57,696 --> 01:28:58,764 KNOWLEDGE OR EXPERIENCE IN A 1703 01:28:58,764 --> 01:28:59,765 PARTICULAR FIELD. 1704 01:28:59,765 --> 01:29:01,533 WE FEEL LIKE THIS IS A WAY 1705 01:29:01,533 --> 01:29:02,801 THAT'S WELL ALIGNED WITH THE 1706 01:29:02,801 --> 01:29:05,270 NEEDS OF OUR LEARNERS TO 1707 01:29:05,270 --> 01:29:06,338 DEMONSTRATE THEY ACQUIRED THE 1708 01:29:06,338 --> 01:29:08,373 NEW KNOWLEDGE OR SKILL THAT 1709 01:29:08,373 --> 01:29:09,241 MIGHT HELP THEM GET THAT NEXT 1710 01:29:09,241 --> 01:29:12,945 GRANT OR NEXT JOB. 1711 01:29:12,945 --> 01:29:14,279 SO LET ME JUST TALK A LITTLE BIT 1712 01:29:14,279 --> 01:29:15,948 MORE ABOUT THE HIGHLIGHTS OF OUR 1713 01:29:15,948 --> 01:29:16,315 WORKSHOPS. 1714 01:29:16,315 --> 01:29:19,818 OUR WORKSHOPS ARE DESIGN TO 1715 01:29:19,818 --> 01:29:22,087 ALLOW THE LEARNERS TO VERY 1716 01:29:22,087 --> 01:29:24,489 RAPIDLY ACQUIRE NEW SKILLS OR 1717 01:29:24,489 --> 01:29:26,325 NEW KNOWLEDGE IMMEDIATELY 1718 01:29:26,325 --> 01:29:27,125 APPLICABLE TO THEIR RESEARCH OR 1719 01:29:27,125 --> 01:29:28,493 PROFESSIONAL NEEDS. 1720 01:29:28,493 --> 01:29:31,196 AS I MENTIONED BRIEFLY 1721 01:29:31,196 --> 01:29:33,298 PREVIOUSLY, THESE ARE TYPICALLY 1722 01:29:33,298 --> 01:29:34,700 LIVE LECTURES AND HANDS ON 1723 01:29:34,700 --> 01:29:36,668 PRACTICE SESSIONS HELD VIA ZOOM. 1724 01:29:36,668 --> 01:29:38,737 MOST ARE RECORDED SO DESIGN TO 1725 01:29:38,737 --> 01:29:39,938 BE HIGHLY FLEXIBLE IF YOU NEED 1726 01:29:39,938 --> 01:29:41,573 TO STEP AWAY TO DO A STEP IN 1727 01:29:41,573 --> 01:29:42,608 YOUR EXPERIMENT, DON'T WORRY, 1728 01:29:42,608 --> 01:29:43,842 YOU CAN ALWAYS COME BACK AND 1729 01:29:43,842 --> 01:29:46,345 VIEW THE LECTURE RECORDING. 1730 01:29:46,345 --> 01:29:48,280 AGAIN, AS I MENTIONED 1731 01:29:48,280 --> 01:29:49,581 PREVIOUSLY, THESE ARE TYPICALLY 1732 01:29:49,581 --> 01:29:53,852 HELD ON CONSECUTIVE WEEKDAYS BUT 1733 01:29:53,852 --> 01:29:58,557 WE HAVE SOME EVENING AND WEEKEND 1734 01:29:58,557 --> 01:30:01,360 AND WE OFFER CEUs AND 1735 01:30:01,360 --> 01:30:01,960 CERTIFICATES OF COMPLETION. 1736 01:30:01,960 --> 01:30:04,229 OUR ACADEMIC COURSES ARE OFFERED 1737 01:30:04,229 --> 01:30:11,803 IN AN ASYNCHRONOUS MODEL BUT NOT 1738 01:30:11,803 --> 01:30:12,437 SELF-P 1739 01:30:12,437 --> 01:30:12,738 SELF-PACED. 1740 01:30:12,738 --> 01:30:15,340 I'LL TALK ABOUT THAT AND THEY'RE 1741 01:30:15,340 --> 01:30:16,808 HIGHLY ACCESSIBLE OR FLEXIBLE 1742 01:30:16,808 --> 01:30:19,611 FOR BUSY PROFESSIONAL. 1743 01:30:19,611 --> 01:30:22,080 ALL OUR INITIATIVES ARE DESIGN 1744 01:30:22,080 --> 01:30:22,748 AROUND YOUR RESEARCH AND 1745 01:30:22,748 --> 01:30:24,750 PROFESSIONAL COMMITMENTS NOT THE 1746 01:30:24,750 --> 01:30:26,451 OTHER WAY AROUND. 1747 01:30:26,451 --> 01:30:30,455 TYPICALLY OUR ACADEMIC COURSES 1748 01:30:30,455 --> 01:30:31,590 ARE ORGANIZED EACH WEEK 1749 01:30:31,590 --> 01:30:33,325 CORRESPOND TO A MODULE AND 1750 01:30:33,325 --> 01:30:35,527 LEARNERS HAVE THE FREEDOM TO LOG 1751 01:30:35,527 --> 01:30:38,497 IN WHEN IT'S CONVENIENT AND 1752 01:30:38,497 --> 01:30:40,032 NAVIGATE FREELY WITHIN EACH 1753 01:30:40,032 --> 01:30:41,933 MODULE TO COMPLETE THEIR 1754 01:30:41,933 --> 01:30:42,567 LEARNING ASSIGNMENTS AND 1755 01:30:42,567 --> 01:30:44,069 INTERACT WITH THEIR TEACHER AND 1756 01:30:44,069 --> 01:30:45,537 OTHER PEERS IN THEIR CLASS AGAIN 1757 01:30:45,537 --> 01:30:47,039 ON A SCHEDULE CONVENIENT FOR 1758 01:30:47,039 --> 01:30:48,340 THEM. 1759 01:30:48,340 --> 01:30:50,942 TYPICALLY, THERE ARE NO REQUIRED 1760 01:30:50,942 --> 01:30:54,346 LIVE SESSIONS EXCEPT ENGLISH AND 1761 01:30:54,346 --> 01:30:55,947 SPANISH SESSIONS BECAUSE IT'S 1762 01:30:55,947 --> 01:30:58,450 IMPORTANT TO BE ABLE TO SPEAK TO 1763 01:30:58,450 --> 01:30:59,785 EACH OTHER AND TEACH EVER. 1764 01:30:59,785 --> 01:31:06,725 THOUGH OUR COURSES ARE ASY 1765 01:31:06,725 --> 01:31:08,860 ASYNCHRONOUS THEY'RE NOT 1766 01:31:08,860 --> 01:31:10,729 SELF-PACED AND THERE'S AN 1767 01:31:10,729 --> 01:31:13,498 INSTRUCTOR AND ENGAGED COMMUNITY 1768 01:31:13,498 --> 01:31:19,438 OF LEARNERS TO HELP WITH THE 1769 01:31:19,438 --> 01:31:20,439 PEER-TO-PEER LEARNING AND AIM TO 1770 01:31:20,439 --> 01:31:21,873 KEEP OUR STUDENT TO TEACHER 1771 01:31:21,873 --> 01:31:23,942 RATIOS LOW SO YOU CAN GET A HIGH 1772 01:31:23,942 --> 01:31:24,443 DEGREE OF PERSONALIZED 1773 01:31:24,443 --> 01:31:30,649 ATTENTION. 1774 01:31:30,649 --> 01:31:31,917 OUR AREAS OF STUDY CORRESPOND TO 1775 01:31:31,917 --> 01:31:33,618 THE NEEDS OF OUR COMMUNITY. 1776 01:31:33,618 --> 01:31:36,822 AS YOU CAN IMAGINE, IT'S THE 1777 01:31:36,822 --> 01:31:38,323 BIOMEDICAL SCIENCES, BIO 1778 01:31:38,323 --> 01:31:39,624 INFORMATICS AND DATA SCIENCE AND 1779 01:31:39,624 --> 01:31:41,993 STATISTICS AND TEST PREP, PUBLIC 1780 01:31:41,993 --> 01:31:43,929 POLICY, PROJECT MANAGEMENT AND 1781 01:31:43,929 --> 01:31:46,531 LEADERSHIP AS YOU CAN SEE HERE. 1782 01:31:46,531 --> 01:31:47,165 TO GIVE YOU A LITTLE BIT OF 1783 01:31:47,165 --> 01:31:49,101 INFORMATION ABOUT OUR ACADEMIC 1784 01:31:49,101 --> 01:31:52,771 TERMS, OUR WORKSHOPS ARE OFFERED 1785 01:31:52,771 --> 01:31:53,972 YEAR ROUND WHILE OUR COURSES 1786 01:31:53,972 --> 01:31:55,107 CORRESPOND TO A MORE ACADEMIC 1787 01:31:55,107 --> 01:31:56,742 CALENDAR YOU MAY BE FAMILIAR 1788 01:31:56,742 --> 01:31:56,942 WITH. 1789 01:31:56,942 --> 01:32:00,145 THERE ARE MORE DEFINED TIME WHEN 1790 01:32:00,145 --> 01:32:02,347 THOSE REGISTRATION PERIODS OPEN 1791 01:32:02,347 --> 01:32:06,518 FOR OUR COURSES BUT WE HAVE TWO 1792 01:32:06,518 --> 01:32:08,553 FALL AND TWO SPRING SESSIONS SO 1793 01:32:08,553 --> 01:32:09,387 LOTS OF OPPORTUNITIES TO GET 1794 01:32:09,387 --> 01:32:12,090 INVOLVED IN THE COURSES. 1795 01:32:12,090 --> 01:32:18,296 I JUST WANT TO HIGHLIGHT A 1796 01:32:18,296 --> 01:32:19,598 PROBLEM OF OUR INITIATIVES 1797 01:32:19,598 --> 01:32:21,833 RELEVANT TO YOU OR TRAINEES IN 1798 01:32:21,833 --> 01:32:24,770 YOUR LAB WE HAVE A MANUSCRIPT 1799 01:32:24,770 --> 01:32:25,904 CITING WORKSHOP THAT WALKS 1800 01:32:25,904 --> 01:32:28,573 THROUGH PREPARING, WRITING, 1801 01:32:28,573 --> 01:32:32,878 SENDING OFF A MANUSCRIPT AND 1802 01:32:32,878 --> 01:32:33,578 RESPOND. 1803 01:32:33,578 --> 01:32:34,846 THIS SAY HIGHLY SUPPORTIVE 1804 01:32:34,846 --> 01:32:35,147 ENVIRONMENT. 1805 01:32:35,147 --> 01:32:36,681 IF YOU HAVE TRAINEES IN YOUR 1806 01:32:36,681 --> 01:32:38,917 LABS WHO MIGHT BE AT THE EARLIER 1807 01:32:38,917 --> 01:32:41,119 STAGES OF DEVELOPING THAT 1808 01:32:41,119 --> 01:32:43,021 EXPERTISE AND MANUSCRIPTS THIS 1809 01:32:43,021 --> 01:32:45,090 MAY BE A GREAT OPTION TO GAIN 1810 01:32:45,090 --> 01:32:45,857 MORE EXPERIENCE AND A LOT OF 1811 01:32:45,857 --> 01:32:49,628 FEEDBACK IN HOW TO PRESENT THAT 1812 01:32:49,628 --> 01:32:50,228 DATA IN THE BEST POSSIBLE WAY. 1813 01:32:50,228 --> 01:32:51,963 AND WE OFFER THIS ONE EVERY 1814 01:32:51,963 --> 01:32:52,831 OTHER MONTH. 1815 01:32:52,831 --> 01:32:56,301 LOTS OF OPPORTUNITIES TO GET 1816 01:32:56,301 --> 01:32:56,735 INVOLVED. 1817 01:32:56,735 --> 01:32:58,870 APOLOGIES THERE'S A TYPO ON THE 1818 01:32:58,870 --> 01:32:59,504 SLIDE. 1819 01:32:59,504 --> 01:33:01,373 THESE ARE OUR 2024 SPRING 1820 01:33:01,373 --> 01:33:01,773 SEMESTER COURSES. 1821 01:33:01,773 --> 01:33:03,308 OUR REGISTRATION IS GETTING TO 1822 01:33:03,308 --> 01:33:06,111 LUNCH AT THE END OF NOVEMBER. 1823 01:33:06,111 --> 01:33:11,283 THESE ARE A SIM SAMPLING OF THE 1824 01:33:11,283 --> 01:33:12,217 OFFERING IN THE SPRING TERM AND 1825 01:33:12,217 --> 01:33:14,619 WILL OVER MORE THAN THIS BUT 1826 01:33:14,619 --> 01:33:16,922 LOTS OF CONTENT IN BIO 1827 01:33:16,922 --> 01:33:19,524 INFORMATICS, STATISTICS, OTHER 1828 01:33:19,524 --> 01:33:21,526 AREAS THAT MAY COMPLIMENT YOUR 1829 01:33:21,526 --> 01:33:22,761 RESEARCH. 1830 01:33:22,761 --> 01:33:23,595 HOPEFULLY BY NOW YOU'RE THINKING 1831 01:33:23,595 --> 01:33:25,630 HOW CAN I REGISTER AND GET THE 1832 01:33:25,630 --> 01:33:27,299 TRAINEES IN MY LABS TO REGISTER 1833 01:33:27,299 --> 01:33:30,202 FOR THOSE COURSES. 1834 01:33:30,202 --> 01:33:36,141 NAVIGATE OVER TO 1835 01:33:36,141 --> 01:33:37,175 EDUCATION.FAS.org AND YOU CAN 1836 01:33:37,175 --> 01:33:39,344 CREATE A LEARNER ACCOUNT AND 1837 01:33:39,344 --> 01:33:41,079 REGISTER. 1838 01:33:41,079 --> 01:33:43,582 WE DO WANT TO EMPHASIZE WHILE WE 1839 01:33:43,582 --> 01:33:45,350 TRY TO KEEP OUR TUITION 1840 01:33:45,350 --> 01:33:47,586 EXTREMELY LOW WE ALSO HAVE 1841 01:33:47,586 --> 01:33:49,688 SCHOLARSHIPS AVAILABLE FOR OUR 1842 01:33:49,688 --> 01:33:50,288 SELF-FUNDING STUDENTS. 1843 01:33:50,288 --> 01:33:52,791 IF YOU ARE FUNDING YOURSELF OR 1844 01:33:52,791 --> 01:33:54,893 IF SOME TRAINEES IN YOUR LABS 1845 01:33:54,893 --> 01:33:56,761 ARE FUNDING THEMSELVES WE 1846 01:33:56,761 --> 01:33:58,063 ENCOURAGE YOU TO TAKE ADVANTAGE 1847 01:33:58,063 --> 01:33:59,931 OF THE SCHOLARSHIP 1848 01:33:59,931 --> 01:34:00,732 OPPORTUNITIES. 1849 01:34:00,732 --> 01:34:03,168 WE DO OFFER A GOVERNMENT 1850 01:34:03,168 --> 01:34:04,402 DISCOUNT FOR ANYBODY FOR WHOM 1851 01:34:04,402 --> 01:34:06,204 THAT APPLIES BUT ALSO WANT TO 1852 01:34:06,204 --> 01:34:07,639 EXPAND OUR GOVERNMENT DISCOUNT 1853 01:34:07,639 --> 01:34:09,374 TO ALL OF YOU WHO MAY BE FROM 1854 01:34:09,374 --> 01:34:10,275 OTHER INSTITUTIONS. 1855 01:34:10,275 --> 01:34:13,144 SO WE'RE OPENING UP OUR 1856 01:34:13,144 --> 01:34:14,012 GOVERNMENT DISCOUNT TO ANYONE 1857 01:34:14,012 --> 01:34:15,747 WHO HAS ATTENDED TODAY. 1858 01:34:15,747 --> 01:34:16,681 SCAN THE QR CODE AND IT WILL 1859 01:34:16,681 --> 01:34:18,283 TAKE YOU TO A FORM TO REQUEST 1860 01:34:18,283 --> 01:34:20,819 THE DISCOUNT CODE TO GET THE 1861 01:34:20,819 --> 01:34:23,955 SAME RATE WHICH IS OUR LOWEST 1862 01:34:23,955 --> 01:34:26,124 RATE WE OFFER TO THE GOVERNMENT. 1863 01:34:26,124 --> 01:34:28,793 NOW, FINALLY, I ALSO WANTED TO 1864 01:34:28,793 --> 01:34:31,796 SHARE WE OFFER OPPORTUNITIES TO 1865 01:34:31,796 --> 01:34:33,131 TEACH AS WELL AS TO GAIN 1866 01:34:33,131 --> 01:34:36,601 TRAINING IN RESEARCH-BASED BEST 1867 01:34:36,601 --> 01:34:37,602 PRACTICES FOR TEACHING. 1868 01:34:37,602 --> 01:34:39,170 SO IF YOU WANT THE OPPORTUNITY 1869 01:34:39,170 --> 01:34:42,674 TO GET INTO ONE OF OUR ONLINE 1870 01:34:42,674 --> 01:34:44,476 CLASSROOMS, BUILD A COURSE AND 1871 01:34:44,476 --> 01:34:45,176 FACILITATE THAT LEARNING 1872 01:34:45,176 --> 01:34:47,946 EXPERIENCE FOR STUDENTS, WE 1873 01:34:47,946 --> 01:34:50,715 WOULD LOVE TO SPEAK WITH YOU 1874 01:34:50,715 --> 01:34:51,583 ABOUT THIS FURTHER. 1875 01:34:51,583 --> 01:34:55,954 SO AGAIN, PLEASE SIMPLY E-MAIL 1876 01:34:55,954 --> 01:35:00,091 US AT REGISTRAR@FAS.org AND TALK 1877 01:35:00,091 --> 01:35:01,593 ABOUT THE TRAINING AND SUPPORT 1878 01:35:01,593 --> 01:35:06,064 WE PROVIDE FOR FACULTY AND 1879 01:35:06,064 --> 01:35:06,765 VARIOUS TRAINING OPPORTUNITIES. 1880 01:35:06,765 --> 01:35:09,167 WE'RE SO HAPPY WE WERE ABLE TO 1881 01:35:09,167 --> 01:35:10,001 PROVIDE SOME SPONSORSHIP FOR 1882 01:35:10,001 --> 01:35:11,002 THIS MEETING AND APPRECIATE THE 1883 01:35:11,002 --> 01:35:12,871 OPPORTUNITY FOR ME TO SHARE WITH 1884 01:35:12,871 --> 01:35:15,006 YOU A LITTLE BIT ABOUT WHO FAS 1885 01:35:15,006 --> 01:35:17,676 IS AND WHAT SOME OF THE 1886 01:35:17,676 --> 01:35:19,945 RESOURCES WE CAN OFFER TO OUR 1887 01:35:19,945 --> 01:35:21,046 SCIENTISTS TO HELP ADVANCE YOUR 1888 01:35:21,046 --> 01:35:25,216 CAREER TO THE NEXT LEVEL. 1889 01:35:25,216 --> 01:35:28,053 PLEASE DON'T HESITATE TO GET IN 1890 01:35:28,053 --> 01:35:29,721 CONTACT AND DROP US AN E-MAIL OR 1891 01:35:29,721 --> 01:35:31,957 PHONE CALL BUT HOPE WE'LL BE 1892 01:35:31,957 --> 01:35:33,391 WELCOMING SOME OF YOU AND SOME 1893 01:35:33,391 --> 01:35:35,860 OF THOSE IN YOUR LAB IN OUR 1894 01:35:35,860 --> 01:35:37,329 WORKSHOPS OR PERHAPS AS A 1895 01:35:37,329 --> 01:35:38,363 FACULTY MEMBER. 1896 01:35:38,363 --> 01:35:39,864 I KNOW YOU'RE READY TO GO TO 1897 01:35:39,864 --> 01:35:42,233 LUNCH BUT ALSO HAPPY TO TAKE 1898 01:35:42,233 --> 01:35:44,102 QUESTIONS IF YOU HAVE SOME AND 1899 01:35:44,102 --> 01:35:53,611 THANK YOU AGAIN. 1900 01:35:53,611 --> 01:35:54,212 >> A QUICK QUESTION. 1901 01:35:54,212 --> 01:35:56,581 YOU MIGHT HAVE MENTIONED IT BUT 1902 01:35:56,581 --> 01:35:58,116 ARE THESE ALSO VIRTUAL COURSES 1903 01:35:58,116 --> 01:35:59,584 OR ALL IN PERSON? 1904 01:35:59,584 --> 01:36:02,387 >> CURRENTLY EVERYTHING IS FULLY 1905 01:36:02,387 --> 01:36:03,254 ONLINE. 1906 01:36:03,254 --> 01:36:04,022 HIGHLY ACCESSIBLE NO MATTER 1907 01:36:04,022 --> 01:36:05,590 WHERE YOU'RE LOCATED. 1908 01:36:05,590 --> 01:36:07,926 >> AMAZING. 1909 01:36:07,926 --> 01:36:11,629 THANK YOU. 1910 01:36:11,629 --> 01:36:13,131 >> ALL RIGHT SO MUCH. 1911 01:36:13,131 --> 01:36:14,366 ENJOY LUNCH. 1912 01:36:14,366 --> 01:36:14,432 1913 01:36:20,472 --> 01:36:21,406 >> THANK YOU VERY MUCH. 1914 01:36:21,406 --> 01:36:25,477 I'D LIKE TO CLOSE THE FIRST 1915 01:36:25,477 --> 01:36:26,578 MORNING SESSION. 1916 01:36:26,578 --> 01:36:29,581 LUNCH IS AVAILABLE UPSTAIRS TO 1917 01:36:29,581 --> 01:36:30,348 MY LEFT. 1918 01:36:30,348 --> 01:36:32,584 THE CAFETERIA IS OPEN. 1919 01:36:32,584 --> 01:36:33,385 THAT'S NEW. 1920 01:36:33,385 --> 01:36:35,954 THE CAFETERIA IS ONLY OPEN FOR 1921 01:36:35,954 --> 01:36:36,221 TODAY. 1922 01:36:36,221 --> 01:36:39,657 AND WE WILL SEE YOU AS WE GET 1923 01:36:39,657 --> 01:36:39,991 BACK AT 1:00. 1924 01:36:39,991 --> 01:36:42,727 ALL RIGHT, THANK YOU VERY MUCH. 1925 01:36:42,727 --> 01:36:42,961 1926 01:36:42,961 --> 01:36:45,430 I'D ALSO LIKE TO THANK ALL THE 1927 01:36:45,430 --> 01:36:46,598 SPEAKERS AND THE LIGHTNING TALK 1928 01:36:46,598 --> 01:36:54,940 PRESENTERS. 1929 01:36:54,940 --> 01:36:59,879 HOPE YOU HAD A GOOD LUNCH BREAK. 1930 01:36:59,879 --> 01:37:04,183 I'M CHIAYENG WANG I'LL BE YOUR 1931 01:37:04,183 --> 01:37:05,551 MODERATOR ON BIOMANUFACTURING 1932 01:37:05,551 --> 01:37:12,585 CASE STUDIES. 1933 01:37:12,585 --> 01:37:15,488 THIS AFTERNOON'S SESSION WILL 1934 01:37:15,488 --> 01:37:18,425 HAVE THREE TALKS IN THE MAIN 1935 01:37:18,425 --> 01:37:21,394 EVENT FOLLOWED BY A POSTER 1936 01:37:21,394 --> 01:37:22,328 QUESTION SOON AFTER WITHIN THE 1937 01:37:22,328 --> 01:37:23,863 MAIN EVENT. 1938 01:37:23,863 --> 01:37:29,302 AND WE WILL HAVE A 45-MINUTE 1939 01:37:29,302 --> 01:37:30,670 BREAK AFTER THE SECOND TALK. 1940 01:37:30,670 --> 01:37:34,941 THE THIRD TALK WILL START AT 1941 01:37:34,941 --> 01:37:36,176 2:45 TO PLEASE REMEMBER TO COME 1942 01:37:36,176 --> 01:37:36,776 BACK. 1943 01:37:36,776 --> 01:37:41,314 DURING THE BREAK, THIS IS MAINLY 1944 01:37:41,314 --> 01:37:42,949 FOR POSTER SETUP. 1945 01:37:42,949 --> 01:37:49,155 NOW, ORIGINALLY WE HAVE DR 1946 01:37:49,155 --> 01:37:55,628 DR. SOLOMON TO DO THE FIRST 1947 01:37:55,628 --> 01:37:57,297 LECTURE BUT SHE HAD DIFFICULTY 1948 01:37:57,297 --> 01:37:59,332 ARRIVING AT THE MAIN CAMPUS AND 1949 01:37:59,332 --> 01:38:01,401 ENCOUNTERED DIFFICULTY IN TERMS 1950 01:38:01,401 --> 01:38:03,636 OF THE ONLINE PRESENTATION SO 1951 01:38:03,636 --> 01:38:06,172 THE I.T. FOLKS ARE GOING TO 1952 01:38:06,172 --> 01:38:07,807 WORKING WITH HER SO WE'RE GOING 1953 01:38:07,807 --> 01:38:11,211 TO HAVE A SWITCH OF THE ORDER OF 1954 01:38:11,211 --> 01:38:11,544 PRESENTATION. 1955 01:38:11,544 --> 01:38:14,748 WE'LL START WITH THE LIGHTNING 1956 01:38:14,748 --> 01:38:15,081 TALK INSTEAD. 1957 01:38:15,081 --> 01:38:18,651 SO OUR LIGHTNING TALK WILL BE 1958 01:38:18,651 --> 01:38:22,722 GIVEN BY DR. MICHAEL MORASKIE A 1959 01:38:22,722 --> 01:38:24,023 Ph.D. CANDIDATE IN THE 1960 01:38:24,023 --> 01:38:31,698 DEPARTMENT OF BIOCHEMISTRY AND 1961 01:38:31,698 --> 01:38:33,099 MOLECULAR BIOLOGY FROM THE 1962 01:38:33,099 --> 01:38:34,400 UNIVERSITY OF MIAMI TALKING 1963 01:38:34,400 --> 01:38:39,105 ABOUT A PLATFORM FOR DETESTING 1964 01:38:39,105 --> 01:38:40,740 FORM SENSING MOLECULES KNOWN TO 1965 01:38:40,740 --> 01:38:44,077 BE PART OF CELL-CELL COMMUNITY 1966 01:38:44,077 --> 01:38:54,254 MECHANISM. 1967 01:38:58,792 --> 01:38:59,259 >> ALL RIGHT. 1968 01:38:59,259 --> 01:39:00,627 HELLO EVERYONE. 1969 01:39:00,627 --> 01:39:03,596 MY NAME IS MICHAEL MORASKIE AND 1970 01:39:03,596 --> 01:39:05,965 HERE TO PRESENT BY WORK 1971 01:39:05,965 --> 01:39:09,068 ILLUMINATING QUORUM FOR THE 1972 01:39:09,068 --> 01:39:10,737 NOVEL CORE SENSING MOLECULE DPO 1973 01:39:10,737 --> 01:39:12,438 AND REVELATIONS FROM THE 1974 01:39:12,438 --> 01:39:16,075 QUANTIFIED PRESENCE IN HUMANS, 1975 01:39:16,075 --> 01:39:19,112 ANIMALS AND BACTERIA. 1976 01:39:19,112 --> 01:39:21,381 SO THROUGHOUT MY Ph.D. JOURNEY 1977 01:39:21,381 --> 01:39:22,816 I'VE COME TO LEARN A LOT ABOUT 1978 01:39:22,816 --> 01:39:23,917 BACTERIAL COMMUNICATION AND 1979 01:39:23,917 --> 01:39:27,620 WITHIN THIS WORLD OF BACTERIAL 1980 01:39:27,620 --> 01:39:28,721 COMMUNICATION WE SORT OF THINK 1981 01:39:28,721 --> 01:39:32,058 ABOUT BACTERIA ENGAGING IN 1982 01:39:32,058 --> 01:39:34,027 BACTERIAL BEHAVIORS ALMOST AND 1983 01:39:34,027 --> 01:39:35,228 SPECIFICALLY TWO KINDS. 1984 01:39:35,228 --> 01:39:40,099 ONE BEHAVIOR TYPE OR I GUESS 1985 01:39:40,099 --> 01:39:42,135 GENETIC PROGRAMMING IN WHICH 1986 01:39:42,135 --> 01:39:43,970 THEY TAKE ON INDIVIDUAL 1987 01:39:43,970 --> 01:39:48,641 BEHAVIORS AT LOW CELL DENSITY. 1988 01:39:48,641 --> 01:39:50,743 PART OF THE GENETIC PROGRAMMING 1989 01:39:50,743 --> 01:39:53,713 DURING THE GENETIC EXPRESSION IS 1990 01:39:53,713 --> 01:39:56,015 THE SYNTHESIS AND RELEASE OF 1991 01:39:56,015 --> 01:39:57,884 SMALL CHEMICAL SIGNALLING 1992 01:39:57,884 --> 01:40:00,320 MOLECULES THAT DIFFUSE INTO THE 1993 01:40:00,320 --> 01:40:01,387 MICROENVIRONMENT. 1994 01:40:01,387 --> 01:40:02,889 YOU CAN IMAGINE AS THE BACTERIA 1995 01:40:02,889 --> 01:40:07,227 BEGIN TO DIVIDE AND GROW, THE 1996 01:40:07,227 --> 01:40:10,730 CONCENTRATION OF THE MOLECULES 1997 01:40:10,730 --> 01:40:11,264 BEGINS TO INCREASE IN THE 1998 01:40:11,264 --> 01:40:13,199 MICROENVIRONMENT. 1999 01:40:13,199 --> 01:40:16,102 THIS SORT OF TRIGGERS A SWITCH 2000 01:40:16,102 --> 01:40:19,272 INTO A GROUP SORT OF BEHAVIOR OR 2001 01:40:19,272 --> 01:40:21,174 GENETIC PROGRAMMING AND 2002 01:40:21,174 --> 01:40:21,608 BACTERIA. 2003 01:40:21,608 --> 01:40:26,346 SO IN ESSENCE THE CELLS ARE 2004 01:40:26,346 --> 01:40:30,149 USING THE SMALL CHEMICAL 2005 01:40:30,149 --> 01:40:32,585 MOLECULE KNOWN AS INDUCERS AS A 2006 01:40:32,585 --> 01:40:34,354 PROXY FOR CELL NUMBER. 2007 01:40:34,354 --> 01:40:35,855 THROUGHOUT THE YEARS AS QUORUM 2008 01:40:35,855 --> 01:40:37,056 SENSING HAS BEEN STUDIED MORE 2009 01:40:37,056 --> 01:40:42,128 AND MORE IT'S BEEN FOUND IT 2010 01:40:42,128 --> 01:40:43,429 TYPICALLY REGULATES BACTERIAL 2011 01:40:43,429 --> 01:40:46,633 BEHAVIORS WITH RELIANCE ON THE 2012 01:40:46,633 --> 01:40:47,800 SYNCHRONIZED EXPRESSION OF 2013 01:40:47,800 --> 01:40:49,836 GENETIC CIRCUITRIES. 2014 01:40:49,836 --> 01:40:55,541 IT WAS ORIGINALLY DISCOVERED IN 2015 01:40:55,541 --> 01:41:06,219 MARINE BIBLIOSPECIES USED TO 2016 01:41:08,888 --> 01:41:10,623 ILLUMENESS AND YOU'D WANT TO 2017 01:41:10,623 --> 01:41:12,992 INITIATE THESE BEHAVIORS ONCE 2018 01:41:12,992 --> 01:41:13,826 YOU HAVE ENOUGH. 2019 01:41:13,826 --> 01:41:18,765 AS WE ALL KNOW, BACTERIAL ARE 2020 01:41:18,765 --> 01:41:19,966 RARELY ISOLATED. 2021 01:41:19,966 --> 01:41:22,735 THEY'RE CONSTANTLY SURROUNDED BY 2022 01:41:22,735 --> 01:41:25,538 OTHER MICROORGANISMS. 2023 01:41:25,538 --> 01:41:27,273 IT TURNS OUT THERE'S BEEN 2024 01:41:27,273 --> 01:41:31,044 DIFFERENT CLASSES OF THESE AUTO 2025 01:41:31,044 --> 01:41:32,045 INDUCERS DISCOVERED THAT 2026 01:41:32,045 --> 01:41:34,681 REGULATE DIFFERENT SORTS OF 2027 01:41:34,681 --> 01:41:35,415 GROUP BEHAVIORS. 2028 01:41:35,415 --> 01:41:38,318 SOME AUTO INDUCERS ARE USED FOR 2029 01:41:38,318 --> 01:41:38,885 INTERSPECIES COMMUNICATION. 2030 01:41:38,885 --> 01:41:44,290 OTHERS HAVE BEEN FOUND USED FOR 2031 01:41:44,290 --> 01:41:45,625 INTERGENUS SPECIES AND 2032 01:41:45,625 --> 01:41:47,827 INTERKINGDOM AND THAT'S A 2033 01:41:47,827 --> 01:41:49,295 FASCINATING ANGLE TO THIS ALL 2034 01:41:49,295 --> 01:41:49,796 RECENTLY. 2035 01:41:49,796 --> 01:41:52,065 THERE'S A LOT OF WORK LOOKING 2036 01:41:52,065 --> 01:41:55,134 INTO VIRAL SPINE OF BACTERIAL 2037 01:41:55,134 --> 01:41:55,768 COMMUNICATION, ESSENTIALLY USING 2038 01:41:55,768 --> 01:41:59,572 THE AUTO INDUCERS TO NUMBER 2039 01:41:59,572 --> 01:42:07,780 THEIR LICENSE MISOGYNY DECISIONS 2040 01:42:07,780 --> 01:42:11,651 AND THE BACTERIAL LANGUAGES THEY 2041 01:42:11,651 --> 01:42:11,884 EMPLOY. 2042 01:42:11,884 --> 01:42:14,787 SO IN THE DONNER LAB WHICH I'M A 2043 01:42:14,787 --> 01:42:16,456 PART OF HAS LONG BEEN INTERESTED 2044 01:42:16,456 --> 01:42:20,860 IN STUDYING THE MICROB BBMICROB. 2045 01:42:20,860 --> 01:42:22,795 THE FIELD HAS EXPLODED RECENTLY 2046 01:42:22,795 --> 01:42:24,797 AND HAVE INCREDIBLE INSIGHT INTO 2047 01:42:24,797 --> 01:42:27,133 HOW MUCH IT REALLY AFFECTS OUR 2048 01:42:27,133 --> 01:42:28,034 OVER ALL HEALTH. 2049 01:42:28,034 --> 01:42:32,638 BUT THE CURRENT STATE OF THE 2050 01:42:32,638 --> 01:42:34,741 FIELD IS LARGELY CORRELATIONAL 2051 01:42:34,741 --> 01:42:36,676 IN NATURE AND THERE'S A 2052 01:42:36,676 --> 01:42:38,344 RECOGNITION THERE NEEDS TO BE 2053 01:42:38,344 --> 01:42:41,214 MORE MECHANISTIC INVESTIGATION 2054 01:42:41,214 --> 01:42:44,017 INTO HOW THE MICROBIOME 2055 01:42:44,017 --> 01:42:44,851 INFLUENCES OUR HEALTH. 2056 01:42:44,851 --> 01:42:46,953 AND THE DONNER LAB IS INTERESTED 2057 01:42:46,953 --> 01:42:48,955 IN LOOKING AT IT THROUGH THE 2058 01:42:48,955 --> 01:42:51,057 LENS OF QUORUM SENSING AND 2059 01:42:51,057 --> 01:42:53,926 STULYING THE DIFFERENT AUTO 2060 01:42:53,926 --> 01:42:54,427 INDUCERS OR DIFFERENT 2061 01:42:54,427 --> 01:42:56,062 COMMUNICATION SIGNALS. 2062 01:42:56,062 --> 01:42:58,765 SPECIFICALLY BECAUSE WE 2063 01:42:58,765 --> 01:43:00,099 UNDERSTAND THAT THESE SMALL 2064 01:43:00,099 --> 01:43:02,201 CHEMICAL MOLECULES TRIGGER 2065 01:43:02,201 --> 01:43:04,070 COMMUNITY-WIDE BEHAVIORS WHICH 2066 01:43:04,070 --> 01:43:08,074 MAY EXPLAIN CHANGES IN MICROBIAL 2067 01:43:08,074 --> 01:43:14,814 THE MAKE UP OF THE MICROBIOME 2068 01:43:14,814 --> 01:43:16,749 COMMUNITIES AND THE QUORUM 2069 01:43:16,749 --> 01:43:20,086 SENSING OF IT ALL THIS IS AN 2070 01:43:20,086 --> 01:43:22,789 OVER SIMPLIFIED VERSION GROUND 2071 01:43:22,789 --> 01:43:25,391 BACTERIA HAVE A SIMPLE CORE 2072 01:43:25,391 --> 01:43:30,363 MECHANISM AND THEY GENERALLY 2073 01:43:30,363 --> 01:43:32,231 HAVE RECEPTOR AND MOLECULE THAT 2074 01:43:32,231 --> 01:43:34,267 WILL BIND TO THE AUTO INDUCER 2075 01:43:34,267 --> 01:43:37,503 AND UPON THAT RECOGNITION IT IN 2076 01:43:37,503 --> 01:43:39,839 TURN TURNS INTO TRANSCRIPTION 2077 01:43:39,839 --> 01:43:42,308 FACTOR WHICH BINDS TO PROMOTER 2078 01:43:42,308 --> 01:43:44,043 REGIONS FOR THE UP REGULATION OR 2079 01:43:44,043 --> 01:43:47,680 DOWN REGULATION OF TARGET GENES. 2080 01:43:47,680 --> 01:43:53,152 THE CIRCUIT LIKE NATURE OF THE 2081 01:43:53,152 --> 01:43:53,753 QUORUM-SENSING COMMUNICATION 2082 01:43:53,753 --> 01:43:54,554 SYSTEMS MAKES THEM QUITE 2083 01:43:54,554 --> 01:43:58,758 AMENABLE TO THE DEVELOPMENT OF 2084 01:43:58,758 --> 01:43:59,392 WHOLESALE BIOSENSORS. 2085 01:43:59,392 --> 01:44:01,661 IF PEOPLE AREN'T FAMILIAR IT 2086 01:44:01,661 --> 01:44:05,198 CONSISTS OF ENGINEERED 2087 01:44:05,198 --> 01:44:06,933 MICROORGANISMS WHICH ARE 2088 01:44:06,933 --> 01:44:09,001 MODIFIED TO PRODUCE A FOREIGN 2089 01:44:09,001 --> 01:44:18,010 PROTEIN WHICH BINDS TO AN ANO 2090 01:44:18,010 --> 01:44:19,812 LYTE OF INTEREST AND THIS RELIES 2091 01:44:19,812 --> 01:44:22,281 ON THE RECOGNITION OF THE 2092 01:44:22,281 --> 01:44:25,651 REGULATORY PROTEIN TO THE A 2093 01:44:25,651 --> 01:44:31,491 ANOLYTE AND ON TOP OF THAT THE 2094 01:44:31,491 --> 01:44:36,963 THERE'S A REPORTER AGENT UNDER 2095 01:44:36,963 --> 01:44:40,099 THE TRANSCRIPTIONAL CONTROL OF A 2096 01:44:40,099 --> 01:44:43,836 PROMOTER REGION WHICH THE 2097 01:44:43,836 --> 01:44:46,772 PROTEIN CAN UPLETTING OR DOWN 2098 01:44:46,772 --> 01:44:50,109 REGULATE THE SYSTEM. 2099 01:44:50,109 --> 01:44:52,545 AND PIVOTING TO MY WORK IN THE 2100 01:44:52,545 --> 01:44:55,481 LAB AND THE DONNER LAB HAS A 2101 01:44:55,481 --> 01:45:02,088 WHOLESALE OF SENSORS FOR AUTO 2102 01:45:02,088 --> 01:45:04,490 INDUCERS AND THERE WAS A PAPER 2103 01:45:04,490 --> 01:45:08,528 PUBLISHED BY BONNIE BASS LEADING 2104 01:45:08,528 --> 01:45:10,329 THE CHARGE IN THE QUORUM SENSING 2105 01:45:10,329 --> 01:45:14,467 WORK AND IDENTIFIED A NOVEL 2106 01:45:14,467 --> 01:45:16,068 QUORUM SENSING MOLECULE IN THIS 2107 01:45:16,068 --> 01:45:26,546 TYPE OF CHOLERA AND WHAT IS 2108 01:45:28,114 --> 01:45:31,751 SPECIFIC ABOUT THIS CIRCUITRY 2109 01:45:31,751 --> 01:45:42,228 AND THE TOOL IS A PYRAZINE 2110 01:45:45,398 --> 01:45:48,401 MOLECULE BUT HAS BIOLOGICAL 2111 01:45:48,401 --> 01:45:48,634 ROLE. 2112 01:45:48,634 --> 01:45:55,942 AND IN BIBLIOCHOLERA IT'S BEEN 2113 01:45:55,942 --> 01:46:02,748 SHOWN TO INDUCE BUT IN THIS CASE 2114 01:46:02,748 --> 01:46:04,217 IT INHIBITS AND THE THOUGHT 2115 01:46:04,217 --> 01:46:05,918 CHOLERA BEING A PATHOGENIC 2116 01:46:05,918 --> 01:46:07,920 BACTERIA AND THE END GOAL IS TO 2117 01:46:07,920 --> 01:46:09,956 BE RELEASED BACK IN THE 2118 01:46:09,956 --> 01:46:10,690 ENVIRONMENT. 2119 01:46:10,690 --> 01:46:15,127 IT'S BELIEVED IT EVOLVED THE 2120 01:46:15,127 --> 01:46:16,762 MECHANISM TO KNOW WE 2121 01:46:16,762 --> 01:46:18,831 SUCCESSFULLY COLONIZED AND DONE 2122 01:46:18,831 --> 01:46:22,768 OR THING SO LET'S GET BACK OUT 2123 01:46:22,768 --> 01:46:23,169 THERE. 2124 01:46:23,169 --> 01:46:24,737 AND THE EXACT BIO SYNTHETIC 2125 01:46:24,737 --> 01:46:28,040 BATHE OF DPO WAS NOT UNDERSTAND 2126 01:46:28,040 --> 01:46:32,078 BUT IT'S AN AMINO ACID AND THE 2127 01:46:32,078 --> 01:46:34,513 HYDROGENASE WAS ALSO A KEY 2128 01:46:34,513 --> 01:46:37,049 ENZYME FOR ITS SYNTHESIS AND 2129 01:46:37,049 --> 01:46:39,151 THAT'S IMPORTANT DOWN STREAM 2130 01:46:39,151 --> 01:46:43,422 BECAUSE THE HYDROGENASE IS A 2131 01:46:43,422 --> 01:46:45,024 HIGHLY CONSERVED ENZYME 2132 01:46:45,024 --> 01:46:46,192 INDICATING OTHER BACTERIA MAY BE 2133 01:46:46,192 --> 01:46:47,760 EMPLOYING THIS QUORUM SENSING 2134 01:46:47,760 --> 01:46:50,129 MOLECULE FOR THEIR OWN PURPOSES. 2135 01:46:50,129 --> 01:46:51,631 ANOTHER THING TO MENTION IS THAT 2136 01:46:51,631 --> 01:46:57,136 IN THE CONTEXT OF THE 2137 01:46:57,136 --> 01:47:00,039 MICROBIOME, THREONINE INHABITS 2138 01:47:00,039 --> 01:47:02,875 THE GUT SO FURTHER SUPPORTING 2139 01:47:02,875 --> 01:47:06,412 THE POSSIBILITY THIS DPO MAY BE 2140 01:47:06,412 --> 01:47:07,380 IMPORTANT IN OTHER BACTERIAL 2141 01:47:07,380 --> 01:47:07,613 SPECIES. 2142 01:47:07,613 --> 01:47:09,315 SO YEAH, THIS PAPER WAS 2143 01:47:09,315 --> 01:47:11,884 PUBLISHED AND WE WERE INTERESTED 2144 01:47:11,884 --> 01:47:13,719 IN DEVELOP WHOLESALE BIO SENSOR 2145 01:47:13,719 --> 01:47:15,254 TO STUDY THIS MOLECULE 2146 01:47:15,254 --> 01:47:15,588 SPECIFICALLY. 2147 01:47:15,588 --> 01:47:18,491 YOU CAN SEE THE CIRCUIT CONSISTS 2148 01:47:18,491 --> 01:47:25,164 OF DPO AND BINDS TO THE PROTEIN 2149 01:47:25,164 --> 01:47:26,899 VQMA TO BIND TO SPECIFIC 2150 01:47:26,899 --> 01:47:29,201 PROMOTER REGION FOR A SILENCING 2151 01:47:29,201 --> 01:47:33,873 RNA AND INHIBITS THE TRANSLATION 2152 01:47:33,873 --> 01:47:36,942 OF THE TRANSCRIPTION FACTOR FOR 2153 01:47:36,942 --> 01:47:38,444 THE FORMATION OF GENES. 2154 01:47:38,444 --> 01:47:42,782 DPO FUNCTIONS TO INHIBIT 2155 01:47:42,782 --> 01:47:43,949 FORMATION IN BIBLIOCHOLERA. 2156 01:47:43,949 --> 01:47:45,718 WE HAD ALL THE INFORMATION WE 2157 01:47:45,718 --> 01:47:48,120 NEEDED TO TRY AND DEVELOP A 2158 01:47:48,120 --> 01:47:50,756 WHOLESALE BIOSENSOR. 2159 01:47:50,756 --> 01:47:53,659 WE HAD OUR ANALYTE OF INTEREST 2160 01:47:53,659 --> 01:47:57,730 AND THE PROMOTER REGION TO WHICH 2161 01:47:57,730 --> 01:48:00,599 THE PROTEIN BOUND UPON BINDING 2162 01:48:00,599 --> 01:48:01,133 DPO. 2163 01:48:01,133 --> 01:48:02,935 SO A LOT OF WORK WENT INTO 2164 01:48:02,935 --> 01:48:07,873 TAKING THESE INDIVIDUAL 2165 01:48:07,873 --> 01:48:13,012 COMPONENTS FROM THE VIBRIO 2166 01:48:13,012 --> 01:48:16,482 CHOLERAE AND THE WAY IT WORKS I 2167 01:48:16,482 --> 01:48:19,752 TOOK THE VQMA PROTEIN PLACED IT 2168 01:48:19,752 --> 01:48:22,788 UNDER THE CONTROL OF THE 2169 01:48:22,788 --> 01:48:24,790 CONSTITUENT PROMOTER AND THEN 2170 01:48:24,790 --> 01:48:29,562 TOOK A BIO LUMINESCENT CASSETTE 2171 01:48:29,562 --> 01:48:32,064 AND PLACED IT UNDER CONTROL OF 2172 01:48:32,064 --> 01:48:34,800 THE PROMOTER WHICH IS WHAT THE 2173 01:48:34,800 --> 01:48:38,537 COMPLEX BINDS TO TO UP REGULATE. 2174 01:48:38,537 --> 01:48:40,106 IN ESSENCE AFTER A LOT OF ASSAY 2175 01:48:40,106 --> 01:48:42,108 OPTIMIZATION WHICH INCLUDED 2176 01:48:42,108 --> 01:48:43,342 FIGURING OUT THE CORRECT OPTICAL 2177 01:48:43,342 --> 01:48:46,679 DENSITY AND INCUBATION TIMES AND 2178 01:48:46,679 --> 01:48:48,614 WHATNOT WE WERE ABLE TO DEVELOP 2179 01:48:48,614 --> 01:48:50,216 A WHOLESALE BIO SENSOR TO 2180 01:48:50,216 --> 01:48:58,758 QUANTIFY THE PRESENCE OF DPO 2181 01:48:58,758 --> 01:48:59,492 BASED ON A BIOLUMINESCENT SIGNAL 2182 01:48:59,492 --> 01:49:02,962 AND THERE'S WORK I'M NOT SHOWING 2183 01:49:02,962 --> 01:49:04,497 ON SHOWING SPECIFICITY. 2184 01:49:04,497 --> 01:49:08,901 I'LL HAVE A POSTER LATER IF 2185 01:49:08,901 --> 01:49:13,472 ANYONE IS CURIOUS IS THAT AND A 2186 01:49:13,472 --> 01:49:20,479 LOT OF WORK WENT INTO CHARACTER 2187 01:49:20,479 --> 01:49:24,250 INTO DETECT THE DPO. 2188 01:49:24,250 --> 01:49:26,051 THE NEXT PHASE SHOWED IT COULD 2189 01:49:26,051 --> 01:49:27,920 BE AN INTERESTING TOOL TO STUDY 2190 01:49:27,920 --> 01:49:32,458 THE MOLECULE. 2191 01:49:32,458 --> 01:49:34,794 AND RESPONSE CURVES ARE 2192 01:49:34,794 --> 01:49:35,928 GENERATED BY COMMERCIALLY 2193 01:49:35,928 --> 01:49:41,400 ACQUIRED DPO. 2194 01:49:41,400 --> 01:49:46,539 SO I TOOK SPENT MEDIA FROM 2195 01:49:46,539 --> 01:49:47,373 VIBRIO CHOLERA AND THE PEOPLE 2196 01:49:47,373 --> 01:49:49,708 WHO DISCOVERED THIS MOLECULE HAD 2197 01:49:49,708 --> 01:49:52,812 INDICATED E. COLI POSSIBLY MADE 2198 01:49:52,812 --> 01:49:53,512 IT AS WELL. 2199 01:49:53,512 --> 01:49:56,949 AND THEY KNOCK OUT A STRAIN OF 2200 01:49:56,949 --> 01:49:59,452 TDH BECAUSE IT'S THE KEY ENZYME 2201 01:49:59,452 --> 01:49:59,985 BORE THE SYNTHESIS. 2202 01:49:59,985 --> 01:50:04,723 TO SHOW WE CAN DETECT IN VITRO 2203 01:50:04,723 --> 01:50:07,993 AND BY CHOLERA AND E. COLI. 2204 01:50:07,993 --> 01:50:09,728 THE NEXT PHASE OF WORK WENT INTO 2205 01:50:09,728 --> 01:50:12,064 GIVEN OUR INTEREST IN STUDYING 2206 01:50:12,064 --> 01:50:14,533 THE MICROBIOME IN THE CONTEXT OF 2207 01:50:14,533 --> 01:50:16,101 THE MICROBIOME WE WANTED TO SEE 2208 01:50:16,101 --> 01:50:18,671 IF WE CAN DETECT THIS MOLECULE 2209 01:50:18,671 --> 01:50:21,540 IN STOOL. 2210 01:50:21,540 --> 01:50:24,076 KNOWING IT HAD BEEN DBO WAS USED 2211 01:50:24,076 --> 01:50:26,178 BY OTHER GRAM NEGATIVE BACTERIA. 2212 01:50:26,178 --> 01:50:30,115 A LOT OF WORK WENT INTO 2213 01:50:30,115 --> 01:50:31,650 DEVELOPING SAMPLE PREPARATION 2214 01:50:31,650 --> 01:50:32,351 PROTOCOL. 2215 01:50:32,351 --> 01:50:34,720 BEING A LIVING SENSOR WE'RE 2216 01:50:34,720 --> 01:50:37,289 LIMITED TO HAVING THE SENSOR BE 2217 01:50:37,289 --> 01:50:46,198 HAPPY, OF COURSE. 2218 01:50:46,198 --> 01:50:50,202 WE TOOK STOOL FROM WILD TYPE AND 2219 01:50:50,202 --> 01:50:53,973 GERM-FREE MICE AND THERE'S A 2220 01:50:53,973 --> 01:50:56,742 SPECTRUM IN WILD TYPE MICE AND 2221 01:50:56,742 --> 01:50:58,911 WE HAVE LITTLE TO NO SIGNAL FROM 2222 01:50:58,911 --> 01:50:59,478 THE SENSOR. 2223 01:50:59,478 --> 01:51:02,748 THEREFORE SUPPORTING THE IDEA 2224 01:51:02,748 --> 01:51:06,151 THAT THIS IS A BACTERIALLY 2225 01:51:06,151 --> 01:51:07,152 DERIVED MOLECULE PRESENT IN THE 2226 01:51:07,152 --> 01:51:08,621 GUT. 2227 01:51:08,621 --> 01:51:12,224 WE NEXT MOVED ON TO OBVIOUSLY WE 2228 01:51:12,224 --> 01:51:13,392 CONDITION SEE IN THE WILD TYPE 2229 01:51:13,392 --> 01:51:14,727 MICE STOOL AND WONDERING IF WE 2230 01:51:14,727 --> 01:51:20,466 CAN SEE IT IN HUMAN TOOL. 2231 01:51:20,466 --> 01:51:22,501 AND THIS IS SHOWING YES, WE CAN 2232 01:51:22,501 --> 01:51:24,603 IN FACT DETECT THIS MOLECULE IN 2233 01:51:24,603 --> 01:51:24,904 STOOL. 2234 01:51:24,904 --> 01:51:27,873 SO THIS WAS PRETTY EXCITING. 2235 01:51:27,873 --> 01:51:29,308 SOME OTHER WORK WENT INTO -- WE 2236 01:51:29,308 --> 01:51:32,778 HAVE SOME WORK LOOKING INTO THE 2237 01:51:32,778 --> 01:51:34,680 ENVIRONMENT ANALYSIS OF 2238 01:51:34,680 --> 01:51:36,048 QUORUM-SENSING MOLECULE I'M NOT 2239 01:51:36,048 --> 01:51:37,816 SHOWING HERE AND ALL TO SAY THIS 2240 01:51:37,816 --> 01:51:40,986 WORK WAS RECENTLY PUBLISHED BACK 2241 01:51:40,986 --> 01:51:44,056 IN JUNE AND CURRENTLY MY WORK IS 2242 01:51:44,056 --> 01:51:47,426 FOCUSSING ON TAKING THIS BIO 2243 01:51:47,426 --> 01:51:49,528 SENSOR AND LOOKING SPECIFICALLY 2244 01:51:49,528 --> 01:51:51,130 AT BACTERIAL STRAINS COMMONLY 2245 01:51:51,130 --> 01:51:52,798 ASSOCIATED WITH TO THE 2246 01:51:52,798 --> 01:51:53,098 MICROBIOME. 2247 01:51:53,098 --> 01:51:54,900 THAT'S BEEN A LOT OF MY WORK 2248 01:51:54,900 --> 01:51:55,701 CURRENTLY. 2249 01:51:55,701 --> 01:51:57,836 WE'RE ALSO INTERESTED IN THE -- 2250 01:51:57,836 --> 01:51:59,538 THE DONNER LAB HAS BEEN 2251 01:51:59,538 --> 01:52:02,308 INTERESTED IN QUORUM SENSING 2252 01:52:02,308 --> 01:52:04,877 MOLECULE AS POTENTIAL BIOMARKERS 2253 01:52:04,877 --> 01:52:07,146 OF CROHN'S DISEASE OR EVEN 2254 01:52:07,146 --> 01:52:07,379 CANCER. 2255 01:52:07,379 --> 01:52:08,080 WE'RE ALSO LOOKING TO EMPLOYEE 2256 01:52:08,080 --> 01:52:10,416 THE SENSOR AND FINALLY WE'RE 2257 01:52:10,416 --> 01:52:11,684 LOOKING TO BUILD A TOOL KIT OF 2258 01:52:11,684 --> 01:52:14,453 BIO SENSORS AS MORE MOLECULE 2259 01:52:14,453 --> 01:52:14,753 DISCOVERED. 2260 01:52:14,753 --> 01:52:18,223 WE CAN START LOOKING AT AUTO 2261 01:52:18,223 --> 01:52:20,059 INDUCER FINGERPRINTS OF 2262 01:52:20,059 --> 01:52:20,659 MICROBIAL COMMUNITIES. 2263 01:52:20,659 --> 01:52:26,899 SO WITH THAT, I'LL FINISH AND 2264 01:52:26,899 --> 01:52:28,000 THANK YOU FOR THE NIH FOR HAVING 2265 01:52:28,000 --> 01:52:29,768 ME AND THANK YOU TO THE DONNER 2266 01:52:29,768 --> 01:52:30,803 DALE GROUP WHERE I'M ONE OF MANY 2267 01:52:30,803 --> 01:52:36,041 IN THE LAB. 2268 01:52:36,041 --> 01:52:39,511 AND SHAMELESSLY PLUG THE FACT 2269 01:52:39,511 --> 01:52:40,913 I'M AIMING TO DEFEND IN MAY. 2270 01:52:40,913 --> 01:52:42,748 MORE THAN HAPPY TO CONNECT. 2271 01:52:42,748 --> 01:52:44,049 WITH THAT I'LL TAKE ANY 2272 01:52:44,049 --> 01:52:54,226 QUESTIONS. 2273 01:53:00,866 --> 01:53:03,802 >> I'LL ASK A COUPLE 2274 01:53:03,802 --> 01:53:07,339 QUESTIONS -- A BIT OF NAIVE 2275 01:53:07,339 --> 01:53:07,606 QUESTIONS. 2276 01:53:07,606 --> 01:53:10,943 FOR THE WHOLESALE BIO SENSOR, TO 2277 01:53:10,943 --> 01:53:14,213 WHAT DEGREE DOES THE SYSTEM 2278 01:53:14,213 --> 01:53:17,516 DIFFERENTIATE VERY CLOSE SIMILAR 2279 01:53:17,516 --> 01:53:19,018 MOLECULES BUT ARE DIFFERENT? 2280 01:53:19,018 --> 01:53:20,386 >> EXCELLENT QUESTION. 2281 01:53:20,386 --> 01:53:23,722 IN MY POSTER, I TESTED A BUNCH 2282 01:53:23,722 --> 01:53:28,694 OF BPO AN LOGS AND IT TURNS OUT 2283 01:53:28,694 --> 01:53:31,163 THEY HAVE NO -- THE SENSOR 2284 01:53:31,163 --> 01:53:33,532 DOESN'T DETECT THEM. 2285 01:53:33,532 --> 01:53:36,068 OBVIOUSLY IT DEPENDS ON THE 2286 01:53:36,068 --> 01:53:37,536 REGULATORY PROTEIN YOU'RE 2287 01:53:37,536 --> 01:53:37,870 EMPLOYING. 2288 01:53:37,870 --> 01:53:39,972 IF IT'S PROMISCUOUS IT CAN BIND 2289 01:53:39,972 --> 01:53:41,306 TO OTHER THINGS AND THAT IN TURN 2290 01:53:41,306 --> 01:53:46,779 CAN BIND TO THE PROMOTER YOU'RE 2291 01:53:46,779 --> 01:53:46,979 USING. 2292 01:53:46,979 --> 01:53:50,449 YOU CAN IN FACT GET A FAULT 2293 01:53:50,449 --> 01:53:52,851 READING AND WE TESTED MOLECULES 2294 01:53:52,851 --> 01:53:54,286 AND DIDN'T GET ANY EFFECT. 2295 01:53:54,286 --> 01:53:58,824 THE CHOLERA IS SPECIFICALLY 2296 01:53:58,824 --> 01:54:02,294 DETECTING DPO SO WE ADOPTED THAT 2297 01:54:02,294 --> 01:54:04,830 FROM THE GENOME AND ANOTHER 2298 01:54:04,830 --> 01:54:09,868 ANGLE TO THAT QUESTION IS THIS 2299 01:54:09,868 --> 01:54:11,170 INTERKINGDOM SIGNALLING AND WE 2300 01:54:11,170 --> 01:54:16,075 FOUND SEROTONIN ACTUALLY 2301 01:54:16,075 --> 01:54:19,445 TRIGGERED A BIOLUMINESCENT 2302 01:54:19,445 --> 01:54:29,988 SIGNAL BASED ON THE CIRCUITRY OF 2303 01:54:34,093 --> 01:54:34,426 PSEUDOMONAS. 2304 01:54:34,426 --> 01:54:35,461 >> ANY SECOND QUESTION AND THIS 2305 01:54:35,461 --> 01:54:38,130 IS A SENSING APPROACH. 2306 01:54:38,130 --> 01:54:46,839 CAN IT BE USED TO IDENTIFY 2307 01:54:46,839 --> 01:54:48,640 EUKARYOTIC MOLECULES MAYBE 2308 01:54:48,640 --> 01:54:52,845 INTERFERING THAT ACTIVATE OR 2309 01:54:52,845 --> 01:54:55,013 INHIBIT BACTERIAL SIGNALLING. 2310 01:54:55,013 --> 01:54:58,050 >> DEFINITELY, YES. 2311 01:54:58,050 --> 01:54:59,885 THE ANGLE I WAS PITCHING WAS 2312 01:54:59,885 --> 01:55:02,821 MORE DPO SPECIFIC BUT WE HAVE A 2313 01:55:02,821 --> 01:55:04,056 NEW Ph.D. STUDENT IN THE LAB 2314 01:55:04,056 --> 01:55:12,064 DOING THAT AND TESTING HORMONES, 2315 01:55:12,064 --> 01:55:15,300 ENDOGENOUS COMPOUNDS AND BECAUSE 2316 01:55:15,300 --> 01:55:17,603 IT WAS FROM VIBRIO CHOLERA THERE 2317 01:55:17,603 --> 01:55:19,805 MAY BE APPROACHES THAT AFFECT 2318 01:55:19,805 --> 01:55:20,105 THE CIRCUIT. 2319 01:55:20,105 --> 01:55:26,178 >> THANK YOU. 2320 01:55:26,178 --> 01:55:29,381 >> SO IF YOU'RE -- YOU HAVE THIS 2321 01:55:29,381 --> 01:55:35,387 SYSTEM THAT IS DEVELOPING VPO, I 2322 01:55:35,387 --> 01:55:35,788 BELIEVE. 2323 01:55:35,788 --> 01:55:37,956 MAYBE YOU COVERED THIS BUT 2324 01:55:37,956 --> 01:55:39,925 WONDERING IF YOU HAVE ANY PLANS 2325 01:55:39,925 --> 01:55:44,062 FOR ESSENTIALLY REWIRING THE 2326 01:55:44,062 --> 01:55:45,497 SYSTEM TO USE THE SAME CIRCUITRY 2327 01:55:45,497 --> 01:55:48,066 EXCEPT TO DETECT SOMETHING ELSE 2328 01:55:48,066 --> 01:55:51,403 IN ORDER TO PRODUCE A DIFFERENT 2329 01:55:51,403 --> 01:55:57,643 RESPONSE AND CHANGE NEG -- 2330 01:55:57,643 --> 01:56:00,512 CHANGING THE INPUT AND OUTPUT IN 2331 01:56:00,512 --> 01:56:01,580 GENERAL. 2332 01:56:01,580 --> 01:56:05,117 >> THAT'S A WHOLE OTHER FIELD OF 2333 01:56:05,117 --> 01:56:11,123 QUORUM SENSING WORK LOOKING INTO 2334 01:56:11,123 --> 01:56:16,061 ESSENTIA 2335 01:56:16,061 --> 01:56:22,868 ESSENTIALLY AND NOT BE ABLE TO 2336 01:56:22,868 --> 01:56:26,805 RECOGNIZE INITIATE VIRULENCE AND 2337 01:56:26,805 --> 01:56:31,176 USING ALTERNATIVES INSTEAD OF 2338 01:56:31,176 --> 01:56:31,476 ANTIBIOTICS. 2339 01:56:31,476 --> 01:56:31,810 >> THANK YOU. 2340 01:56:31,810 --> 01:56:32,177 >> YOU GOT IT. 2341 01:56:32,177 --> 01:56:41,720 THANK YOU, EVERYONE. 2342 01:56:41,720 --> 01:56:42,955 >> OKAY. 2343 01:56:42,955 --> 01:56:48,060 SO WE'RE ALL SET FOR -- OKAY, 2344 01:56:48,060 --> 01:56:52,097 FOR DR. RACHELLE SOLOMON'S 2345 01:56:52,097 --> 01:56:54,299 LECTURE AND SHE'S GOING TO GIVE 2346 01:56:54,299 --> 01:56:55,767 IT ONLINE. 2347 01:56:55,767 --> 01:57:00,038 SHE IS A SENIOR INVESTIGATOR OF 2348 01:57:00,038 --> 01:57:03,809 THE METABOLIC EPIDEMIOLOGY 2349 01:57:03,809 --> 01:57:06,411 BRANCH IN THE DIVISION OF CANCER 2350 01:57:06,411 --> 01:57:09,414 EPIDEMIOLOGY AND GENETICS AT THE 2351 01:57:09,414 --> 01:57:10,849 NATIONAL CANCER INSTITUTE AND 2352 01:57:10,849 --> 01:57:15,988 SHE WILL TELL US ABOUT THE BIO 2353 01:57:15,988 --> 01:57:16,855 MANUFACTURING AT THE FREDERICK 2354 01:57:16,855 --> 01:57:27,199 NATIONAL LABORATORY. 2355 01:58:04,102 --> 01:58:14,346 >> GOOD AFTERNOON. 2356 01:58:15,213 --> 01:58:16,048 ALL RIGHT. 2357 01:58:16,048 --> 01:58:24,022 SO THANK YOU IS THERE SOME 2358 01:58:24,022 --> 01:58:28,093 FEEDBACK OR IS THIS OKAY? 2359 01:58:28,093 --> 01:58:28,327 >> OKAY. 2360 01:58:28,327 --> 01:58:31,263 >> GREAT. 2361 01:58:31,263 --> 01:58:33,899 GOOD AFTERNOON. 2362 01:58:33,899 --> 01:58:38,236 THANK YOU VERY MUCH FOR THE 2363 01:58:38,236 --> 01:58:42,574 INTRODUCTION DR. WANG AND I'M 2364 01:58:42,574 --> 01:58:48,080 GRATEFUL TO THE ORGANIZERS FOR 2365 01:58:48,080 --> 01:58:52,551 INVITING ME TO SHARE WHAT OUR 2366 01:58:52,551 --> 01:58:58,256 GROUP IS DOING IN FREDERICK TO 2367 01:58:58,256 --> 01:58:59,591 ADVANCE CANCER CELL THERAPY. 2368 01:58:59,591 --> 01:59:00,792 WHAT WE'RE DOING AND WHAT I'M 2369 01:59:00,792 --> 01:59:04,796 GOING TO TALK ABOUT TODAY IS THE 2370 01:59:04,796 --> 01:59:09,434 WORK WE ARE DOING TO TACKLE 2371 01:59:09,434 --> 01:59:10,635 HURDLES OF MANUFACTURING 2372 01:59:10,635 --> 01:59:20,212 ENGINEERED T CELLS FOR PATIENTS. 2373 01:59:20,212 --> 01:59:20,412 OKAY. 2374 01:59:20,412 --> 01:59:23,782 SO FOR THOSE WHO ARE NOT 2375 01:59:23,782 --> 01:59:25,817 FAMILIAR WITH THE FREDERICK 2376 01:59:25,817 --> 01:59:30,422 NATIONAL LABS FOR CANCER 2377 01:59:30,422 --> 01:59:33,191 RESEARCH OR ALSO CALLED SNLCR, 2378 01:59:33,191 --> 01:59:34,626 THESE ARE FEDERALLY FUNDED 2379 01:59:34,626 --> 01:59:39,498 RESEARCH AND IT'S A FEDERALLY 2380 01:59:39,498 --> 01:59:40,899 FUNDED RESEARCH AND DEVELOPMENT 2381 01:59:40,899 --> 01:59:42,367 CENTER SUPPORTED PRIMARILY BY 2382 01:59:42,367 --> 01:59:43,535 NCI. 2383 01:59:43,535 --> 01:59:48,573 THEY WERE ORIGINALLY FOUNDED IN 2384 01:59:48,573 --> 01:59:50,175 1972 AND LOTS OF CHANGES HAVE 2385 01:59:50,175 --> 01:59:51,910 OCCURRED. 2386 01:59:51,910 --> 02:00:02,254 THE CURRENT CONTRACTOR WHO IS 2387 02:00:02,254 --> 02:00:04,890 STAFFING IS LITUS MEDICAL 2388 02:00:04,890 --> 02:00:09,761 RESEARCH INCORPORATED. 2389 02:00:09,761 --> 02:00:18,703 AND WHAT THE FNLCR RESPONDS 2390 02:00:18,703 --> 02:00:23,675 QUICKLY TO QUICK LY TO 2391 02:00:23,675 --> 02:00:24,309 CHALLENGES. 2392 02:00:24,309 --> 02:00:25,410 I WON'T GO INTO EVERYTHING 2393 02:00:25,410 --> 02:00:30,582 THAT'S GOING ON IN FREDERICK 2394 02:00:30,582 --> 02:00:31,850 BECAUSE THERE'S SO MUCH WORK I 2395 02:00:31,850 --> 02:00:35,420 ENCOURAGE YOU TO GO TO 2396 02:00:35,420 --> 02:00:36,555 FREDERICK.CANCER.gov TO LEARN 2397 02:00:36,555 --> 02:00:40,125 MORE ABOUT THE WORK GOING ON 2398 02:00:40,125 --> 02:00:50,535 THERE AND THE SERVICES. 2399 02:00:52,938 --> 02:00:58,877 SO WHAT I'M GOING TO TALK ABOUT 2400 02:00:58,877 --> 02:01:00,479 IS THE BIOPHARMACEUTICAL PROGRAM 2401 02:01:00,479 --> 02:01:05,717 FUNDED BY NCI. 2402 02:01:05,717 --> 02:01:09,187 IN PARTICULAR BY THE DIVISION OF 2403 02:01:09,187 --> 02:01:13,625 CANCER DIAGNOSIS AND IT'S LED BY 2404 02:01:13,625 --> 02:01:23,435 JIM DOROWSHOW AND THIS 2405 02:01:23,435 --> 02:01:25,470 MANUFACTURING RESOURCE IS 2406 02:01:25,470 --> 02:01:32,043 OVERSEEN BY THE DEVELOPMENTAL 2407 02:01:32,043 --> 02:01:33,845 THERAPEUTICS PROGRAM AND THE 2408 02:01:33,845 --> 02:01:35,981 GROUP I'M IN CALLED THE 2409 02:01:35,981 --> 02:01:37,449 BIOLOGICAL RESOURCES BRANCH OR 2410 02:01:37,449 --> 02:01:43,655 BRB WHICH IS LED BY DR. JASON 2411 02:01:43,655 --> 02:01:48,059 YOVANDICH WE HAVE THE TASK OF 2412 02:01:48,059 --> 02:01:51,796 OVERSEEING THE WORKSHOP IS DONE 2413 02:01:51,796 --> 02:01:52,898 AT THE BIOPHARMACEUTICAL 2414 02:01:52,898 --> 02:01:57,769 DEVELOPMENT PROGRAM. 2415 02:01:57,769 --> 02:02:03,842 SO ON THE NEXT SLIDE WHAT I AM 2416 02:02:03,842 --> 02:02:08,046 SHOWING AGAIN IS THAT THESE 2417 02:02:08,046 --> 02:02:10,882 UNIQUE RESOURCES AT FREDERICK 2418 02:02:10,882 --> 02:02:16,655 HAS COMPLEXITY THEY'RE FUNDED BY 2419 02:02:16,655 --> 02:02:17,355 NCI. 2420 02:02:17,355 --> 02:02:20,258 THE OPERATION OF THE BDP PROGRAM 2421 02:02:20,258 --> 02:02:23,828 ITSELF IS THAT IT IS STAFFED AND 2422 02:02:23,828 --> 02:02:31,603 MANAGED BY CONTRACTORS FROM 2423 02:02:31,603 --> 02:02:35,307 LEIDOS AND UNIQUELY LOCATED AT 2424 02:02:35,307 --> 02:02:41,379 FREDERICK AT THE FNLCR. 2425 02:02:41,379 --> 02:02:45,083 THEIR MISSION SO NOVEL 2426 02:02:45,083 --> 02:02:46,084 THERAPEUTICS OF TREATMENT OF 2427 02:02:46,084 --> 02:02:48,220 CANCER AND OTHER DISEASE. 2428 02:02:48,220 --> 02:02:50,188 THIS IS BY PROVIDING 2429 02:02:50,188 --> 02:02:51,189 MANUFACTURING, PROCESS DEVELOP. 2430 02:02:51,189 --> 02:02:57,495 PROCESS ANALYTICS AND QUALITY 2431 02:02:57,495 --> 02:02:58,797 ASSURANCE CAPABILITIES AND 2432 02:02:58,797 --> 02:03:08,974 EXPERTISE. 2433 02:03:12,143 --> 02:03:13,445 THEY'VE DEVELOPED FIRST IN CLASS 2434 02:03:13,445 --> 02:03:16,047 PRODUCTS AND THINGS THAT HAVE 2435 02:03:16,047 --> 02:03:21,519 COMPLEX REGULATORY CHALLENGES 2436 02:03:21,519 --> 02:03:22,454 AND OFTEN SELECTED. 2437 02:03:22,454 --> 02:03:29,394 IF WE GO TO THE NEXT SLIDE YOU 2438 02:03:29,394 --> 02:03:32,063 CAN SEE HIGHLIGHTS OF THE 2439 02:03:32,063 --> 02:03:36,067 CAPABILITIES OF THE BDP AND 2440 02:03:36,067 --> 02:03:41,539 THOSE ARE PROCESS DEVELOPMENT 2441 02:03:41,539 --> 02:03:43,775 GMP MANUFACTURING CAPABILITIES 2442 02:03:43,775 --> 02:03:47,579 AND TESTING AND RELEASE OF 2443 02:03:47,579 --> 02:03:50,649 BIOLOGICS. 2444 02:03:50,649 --> 02:03:52,617 WE HAVE A VERY STRONG PROCESS 2445 02:03:52,617 --> 02:03:57,455 ANALYTICS AND QUALITY CONTROL 2446 02:03:57,455 --> 02:04:01,092 PROGRAM WHICH IS CRITICAL IN 2447 02:04:01,092 --> 02:04:04,062 DEVELOPING ASSAYS AND TESTING OF 2448 02:04:04,062 --> 02:04:06,631 THE BIOLOGIC PRODUCTS. 2449 02:04:06,631 --> 02:04:09,534 AND THEN WE ALSO HAVE QUALITY 2450 02:04:09,534 --> 02:04:14,639 ASSURANCE OVERSIGHT WHICH REALLY 2451 02:04:14,639 --> 02:04:19,944 IS CRITICAL BECAUSE THIS ENSURES 2452 02:04:19,944 --> 02:04:22,914 GMP COMPLIANCE AND THE OVER ALL 2453 02:04:22,914 --> 02:04:28,086 QUALITY OF THE SYSTEMS AND THE 2454 02:04:28,086 --> 02:04:30,488 PRODUCTS THAT WE PRODUCE. 2455 02:04:30,488 --> 02:04:32,991 ALONG WITH THAT WE HAVE GREAT 2456 02:04:32,991 --> 02:04:34,793 REGULATORY AFFAIRS SUPPORT WHICH 2457 02:04:34,793 --> 02:04:40,098 HELP IN THE FILING OF THESE 2458 02:04:40,098 --> 02:04:44,069 NOVEL DRUGS FOR I.N.D.s FOR 2459 02:04:44,069 --> 02:04:50,775 CLINICAL TRIALS. 2460 02:04:50,775 --> 02:04:56,081 BDP DOES COMPLY WITH FDA 2461 02:04:56,081 --> 02:04:58,917 REGULATIONS AND STANDARDS 2462 02:04:58,917 --> 02:05:05,223 INCLUDING THE 21CFR CODES. 2463 02:05:05,223 --> 02:05:07,926 SO WHAT DO WE PRODUCE THERE? 2464 02:05:07,926 --> 02:05:10,895 WE PRODUCE ALL TYPES OF 2465 02:05:10,895 --> 02:05:14,032 BIOLOGICS FOR EXAMPLE, 2466 02:05:14,032 --> 02:05:15,667 MONOCLONAL ANTIBODIES, 2467 02:05:15,667 --> 02:05:16,601 RECOMBINANT PROTEINS AND VIRAL 2468 02:05:16,601 --> 02:05:19,237 AND DNA VACCINES, PEPTIDES AND 2469 02:05:19,237 --> 02:05:23,942 GENE THERAPY PRODUCTS. 2470 02:05:23,942 --> 02:05:28,079 AND WHAT I'M TALKING ABOUT TODAY 2471 02:05:28,079 --> 02:05:32,717 IN PARTICULAR IS AN AREA WE JUST 2472 02:05:32,717 --> 02:05:34,386 CAME INTO A FEW YEARS AGO WHY IS 2473 02:05:34,386 --> 02:05:39,524 IS THE PRODUCTION OF CELL-BASED 2474 02:05:39,524 --> 02:05:39,791 PRODUCTS. 2475 02:05:39,791 --> 02:05:40,925 ONE INTERESTING THING TO NOTE 2476 02:05:40,925 --> 02:05:44,095 FOR FOLKS INTERESTED IN LOOKING 2477 02:05:44,095 --> 02:05:47,832 INTO THE BDP IF YOU GO TO THE 2478 02:05:47,832 --> 02:05:51,803 FREDERICK WEBSITE YOU CAN SEE 2479 02:05:51,803 --> 02:05:55,673 LINKS DIRECTLY TO THE BDP BUT 2480 02:05:55,673 --> 02:06:01,379 PROVIDE MANY SERVICES INCLUDING 2481 02:06:01,379 --> 02:06:04,516 GMP TRAINING OF STAFF AND ALSO 2482 02:06:04,516 --> 02:06:08,720 FOR OTHER AGENCIES AND HAVE ALSO 2483 02:06:08,720 --> 02:06:14,192 BEEN OPPOSED AS THE TRAINING 2484 02:06:14,192 --> 02:06:23,802 SITE FOR SO WE HAVE A UNIQUE 2485 02:06:23,802 --> 02:06:28,473 PROCESS IN THAT ALL OF THE SOPs 2486 02:06:28,473 --> 02:06:31,209 THAT THE BDP HAS ARE MADE 2487 02:06:31,209 --> 02:06:33,978 PUBLICLY AVAILABLE. 2488 02:06:33,978 --> 02:06:35,780 IF YOU GO TO THE WEBSITE YOU'LL 2489 02:06:35,780 --> 02:06:40,084 BE ABLE TO SEE SOPs THAT CAN 2490 02:06:40,084 --> 02:06:46,090 POTENTIALLY HELP YOUR WORK. 2491 02:06:46,090 --> 02:06:52,063 ORE THE YEARS THE BDP HAS 2492 02:06:52,063 --> 02:06:52,964 MANUFACTU 2493 02:06:52,964 --> 02:06:54,732 MANUFACTURED MANY LOTS OF OVER 2494 02:06:54,732 --> 02:07:00,071 100 DIFFERENT PRODUCT HAVE GONE 2495 02:07:00,071 --> 02:07:03,308 TO CLINICAL TRIALS AND I THINK 2496 02:07:03,308 --> 02:07:06,110 THERE ARE TWO PRODUCTS THAT HAVE 2497 02:07:06,110 --> 02:07:10,014 BEEN LICENSED BUT THAT IS NOT 2498 02:07:10,014 --> 02:07:10,849 OUR AREA. 2499 02:07:10,849 --> 02:07:13,284 WE ARE NOT TRYING TO LICENSE 2500 02:07:13,284 --> 02:07:13,618 PRODUCTS. 2501 02:07:13,618 --> 02:07:15,920 WE ARE SIMPLY TRYING TO BRIDGE 2502 02:07:15,920 --> 02:07:17,021 THAT GAP TO GET PRODUCTS TO THE 2503 02:07:17,021 --> 02:07:22,694 CLINIC. 2504 02:07:22,694 --> 02:07:33,204 AND SO, YOU'LL SEE THE NCI IS 2505 02:07:35,974 --> 02:07:37,108 FOCUSSED ON SUPPORTING PRODUCT 2506 02:07:37,108 --> 02:07:37,408 DEVELOPMENT. 2507 02:07:37,408 --> 02:07:41,379 IN PARTICULAR, THIS IS ONE OF 2508 02:07:41,379 --> 02:07:43,681 THE REASONS WHY RESOURCES LIKE 2509 02:07:43,681 --> 02:07:50,188 THE BDP ARE AVAILABLE. 2510 02:07:50,188 --> 02:07:53,258 AS YOU KNOW MANY IN OUR AUDIENCE 2511 02:07:53,258 --> 02:07:54,292 ARE FROM BASIC RESEARCH 2512 02:07:54,292 --> 02:07:55,460 LABORATORIES AND SOME ARE 2513 02:07:55,460 --> 02:08:00,832 FURTHER DOWN THE TRANSLATIONAL 2514 02:08:00,832 --> 02:08:01,232 PIPELINE. 2515 02:08:01,232 --> 02:08:02,700 BUT WE KNOW THAT PRODUCT 2516 02:08:02,700 --> 02:08:03,501 DEVELOPMENT CAN BE VERY 2517 02:08:03,501 --> 02:08:07,639 CHALLENGING IN THAT IT REALLY 2518 02:08:07,639 --> 02:08:09,741 REQUIRES A PARADIGM SHIFT TO 2519 02:08:09,741 --> 02:08:10,942 ADVANCE A PRODUCT FROM THE BENCH 2520 02:08:10,942 --> 02:08:15,513 TO THE CLINIC. 2521 02:08:15,513 --> 02:08:20,451 THAT IS DONE BY A CHANGE IN MIND 2522 02:08:20,451 --> 02:08:22,253 SET WHERE YOU'RE GOING FROM 2523 02:08:22,253 --> 02:08:23,521 BASIC RESEARCH HYPOTHESIS DRIVEN 2524 02:08:23,521 --> 02:08:26,958 TO A PARADIGM IN WHICH YOU'RE 2525 02:08:26,958 --> 02:08:28,059 ENGINEERING A PRODUCT WITH THE 2526 02:08:28,059 --> 02:08:30,194 END IN MIND. 2527 02:08:30,194 --> 02:08:31,596 AND THE END BEING GETTING TO THE 2528 02:08:31,596 --> 02:08:35,366 CLINIC AND GETTING TO THE 2529 02:08:35,366 --> 02:08:36,034 PATIENTS. 2530 02:08:36,034 --> 02:08:38,269 AND WHAT WE FIND IS THAT 2531 02:08:38,269 --> 02:08:44,943 RESOURCES LIKE THE BDP ARE VERY 2532 02:08:44,943 --> 02:08:46,978 USEFUL IN THAT PRODUCT 2533 02:08:46,978 --> 02:08:47,679 DEVELOPMENT PATHWAY. 2534 02:08:47,679 --> 02:08:51,549 AND SO IF WE LOOK ON THE NEXT 2535 02:08:51,549 --> 02:08:52,617 SLIDE THIS IS SOMETHING THAT 2536 02:08:52,617 --> 02:08:55,486 MANY OF YOU MAY BE FAMILIAR WITH 2537 02:08:55,486 --> 02:08:57,889 WHICH IS THAT THE PATHWAY TO THE 2538 02:08:57,889 --> 02:09:03,294 CLINIC IS CHALLENGING AND THAT'S 2539 02:09:03,294 --> 02:09:05,763 WHERE THE EXPERTISE OF THE BDP 2540 02:09:05,763 --> 02:09:11,536 AND OTHER RESOURCES ARE REALLY 2541 02:09:11,536 --> 02:09:19,410 IMPORTANT BECAUSE WE OFTEN HAVE 2542 02:09:19,410 --> 02:09:23,014 AN EXPECTATION THE PATH IS 2543 02:09:23,014 --> 02:09:25,883 STRAIGHTFORWARD AND LINEAR AND 2544 02:09:25,883 --> 02:09:26,551 INVESTIGATORS MAY COME IN AND 2545 02:09:26,551 --> 02:09:29,187 SAY I KNOW WHAT I WANT TO DO TO 2546 02:09:29,187 --> 02:09:34,959 GET THIS ANTIBODY TO THE CLINIC 2547 02:09:34,959 --> 02:09:43,868 AND THERE'S MANY CHEMICALS IN 2548 02:09:43,868 --> 02:09:48,573 BIOMANUFACTURING SO IT'S 2549 02:09:48,573 --> 02:09:53,511 CHALLENGING BUT FORTUNATE LY FO 2550 02:09:53,511 --> 02:09:56,347 RESOURCE IS TO HELP IN THE 2551 02:09:56,347 --> 02:10:00,485 PROCESS. 2552 02:10:00,485 --> 02:10:04,422 AND I WAS EXCITED TO PARTICIPATE 2553 02:10:04,422 --> 02:10:08,059 IN THIS MEETING BECAUSE WHAT WE 2554 02:10:08,059 --> 02:10:11,696 ARE SEEING IS THAT AND WHAT I'VE 2555 02:10:11,696 --> 02:10:16,768 APPRECIATED FROM THE PREVIOUS 2556 02:10:16,768 --> 02:10:26,344 TALKS AND WHAT THE ORGANIZERS 2557 02:10:26,344 --> 02:10:27,879 PUT TOGETHER IS THE SYNTHETIC 2558 02:10:27,879 --> 02:10:28,980 BIOLOGY AND PRODUCT MESH WELL 2559 02:10:28,980 --> 02:10:36,054 TOGETHER AND HAVE THIS OVERLAP 2560 02:10:36,054 --> 02:10:37,488 WHERE WE KNOW PRODUCT 2561 02:10:37,488 --> 02:10:42,193 DEVELOPMENT INVOLVES ENGINEERING 2562 02:10:42,193 --> 02:10:46,964 OF A QUALITY PRODUCT THE 2563 02:10:46,964 --> 02:10:48,066 MANUFACTURING PROCESS TO ENSURE 2564 02:10:48,066 --> 02:10:52,070 YOU CONSISTENTLY GET A HIGH 2565 02:10:52,070 --> 02:10:52,637 QUALITY PRODUCTION OF YOUR 2566 02:10:52,637 --> 02:10:58,976 PRODUCT. 2567 02:10:58,976 --> 02:11:03,314 SIMILARLY SYNTHETIC BIOLOGY SAY 2568 02:11:03,314 --> 02:11:07,618 FIELD IN WHICH AIMS TO ENGINEER 2569 02:11:07,618 --> 02:11:08,686 MOLECULES AND CELLS AND 2570 02:11:08,686 --> 02:11:12,056 ORGANISMS WITH NEW FUNCTIONS. 2571 02:11:12,056 --> 02:11:16,060 THE KEY IS THE ENGINEERING MIND 2572 02:11:16,060 --> 02:11:19,664 SET AND WHAT NCI DID WAS 2573 02:11:19,664 --> 02:11:22,500 LEVERAGE THE PRODUCT DEVELOPMENT 2574 02:11:22,500 --> 02:11:26,871 EXPERTISE THAT HAS BEEN AT THE 2575 02:11:26,871 --> 02:11:30,508 BDP MANY YEARS AND USE THAT TO 2576 02:11:30,508 --> 02:11:34,979 ADDRESS THESE NEW MANUFACTURING 2577 02:11:34,979 --> 02:11:36,981 HURDLES THAT COME UP BECAUSE OF 2578 02:11:36,981 --> 02:11:37,381 SYNTHETIC BIOLOGY. 2579 02:11:37,381 --> 02:11:42,887 IN PARTICULAR WHAT I'M TALKING 2580 02:11:42,887 --> 02:11:47,458 ABOUT HERE IS MANUFACTURING OF 2581 02:11:47,458 --> 02:11:49,560 ENGINEERED CELLS FOR PATIENTS. 2582 02:11:49,560 --> 02:11:52,330 WE ENTERED THE FEEL BY FIRST 2583 02:11:52,330 --> 02:11:58,970 GOING -- WORKING TOWARDS MAKING 2584 02:11:58,970 --> 02:12:02,807 ENGINEERED CHIMERIC ANTIGEN 2585 02:12:02,807 --> 02:12:04,142 RECEPTORS OR CARS FOR T CELLS 2586 02:12:04,142 --> 02:12:07,044 AND THOSE RECEPTORS WILL ALLOW A 2587 02:12:07,044 --> 02:12:10,982 T CELL TO TARGET AN ANTIGEN, 2588 02:12:10,982 --> 02:12:12,049 BECOME ACTIVATED AND ALSO BECOME 2589 02:12:12,049 --> 02:12:19,056 ELIMINATED. 2590 02:12:19,056 --> 02:12:23,394 THIS IS A PROCESS WHERE IT'S A 2591 02:12:23,394 --> 02:12:24,762 UNIQUE MANUFACTURING PARADIGM 2592 02:12:24,762 --> 02:12:28,366 WHERE YOU ARE KIND OF IN A RACE 2593 02:12:28,366 --> 02:12:31,803 TO TAKE THE STARTING MATERIAL 2594 02:12:31,803 --> 02:12:42,346 WHICH IS THE PATIENT'S AFOREESE 2595 02:12:42,346 --> 02:12:46,984 -- AND GET THEM BACK TO THE 2596 02:12:46,984 --> 02:12:55,226 PATIENT IS IN NEED OF THE CELLS. 2597 02:12:55,226 --> 02:13:00,064 AND WE WERE LOOKING AT PRODUCT 2598 02:13:00,064 --> 02:13:01,332 DEVELOPMENT AND SYNTHETIC 2599 02:13:01,332 --> 02:13:11,843 BIOLOGY ENERGYING TO ADDRESS 2600 02:13:12,443 --> 02:13:16,981 MANUFACTURING CARS. 2601 02:13:16,981 --> 02:13:22,320 WHAT WE SEE IS AGAIN WE 2602 02:13:22,320 --> 02:13:26,090 LEVERAGED THE EXPERIENCED STAFF 2603 02:13:26,090 --> 02:13:28,960 AND THE EXISTING CGMP 2604 02:13:28,960 --> 02:13:33,197 MANUFACTURING FACILITIES AND 2605 02:13:33,197 --> 02:13:38,436 PROCESSES AND PUT IN PLACE PUT 2606 02:13:38,436 --> 02:13:44,041 IN PLACE A CLOSED AND AUTOMATED 2607 02:13:44,041 --> 02:13:47,445 MANUFACTURING SYSTEMS THAT COULD 2608 02:13:47,445 --> 02:13:49,547 MAKE THESE AND WERE ABLE TO PUT 2609 02:13:49,547 --> 02:13:55,219 IN PLACE PROCESS VALIDATIONS, 2610 02:13:55,219 --> 02:13:56,053 ASSAY DEVELOPMENT AND WHICH IS 2611 02:13:56,053 --> 02:13:57,188 VERY IMPORTANT TO LOOK AT THE 2612 02:13:57,188 --> 02:14:02,827 QUALITY OF THE PRODUCTS THAT 2613 02:14:02,827 --> 02:14:07,899 YOU'RE PRODUCING THIS HAS BEEN 2614 02:14:07,899 --> 02:14:08,933 LACKING IN THE CELL THERAPY 2615 02:14:08,933 --> 02:14:16,073 FIELD IN THAT IT'S CHALLENGING 2616 02:14:16,073 --> 02:14:18,075 TO A CONSISTENT QUALITY. 2617 02:14:18,075 --> 02:14:19,510 SOMETIMES THESE WERE BEING DONE 2618 02:14:19,510 --> 02:14:25,216 IN SMALL ACADEMIC CENTERS OR 2619 02:14:25,216 --> 02:14:31,088 EVEN LARGE ONES BUT IN 2620 02:14:31,088 --> 02:14:33,991 FACILITIES THAT WEREN'T 2621 02:14:33,991 --> 02:14:34,825 NECESSARILY EXPERIENCED IN THE 2622 02:14:34,825 --> 02:14:36,494 HIGH QUALITY PROCESSES 2623 02:14:36,494 --> 02:14:37,495 ASSOCIATED WITH GMP. 2624 02:14:37,495 --> 02:14:46,871 WE WERE ABLE TO PUT IN PLACE 2625 02:14:46,871 --> 02:14:48,673 SYSTEMS TO DO RAPID PRODUCT 2626 02:14:48,673 --> 02:14:49,373 RELEASE AND GETTING THEM BACK TO 2627 02:14:49,373 --> 02:14:58,683 THE PATIENT VERY IMPORTANT. 2628 02:14:58,683 --> 02:15:04,789 WE WERE ABLE TO LOOK AT THE 2629 02:15:04,789 --> 02:15:09,827 LOGISTICS THAT ARE COMPLEX AND 2630 02:15:09,827 --> 02:15:10,528 ASSOCIATED WITH PUTTING THOSE IN 2631 02:15:10,528 --> 02:15:15,166 PLACE SO WE WOULD BE ABLE TO 2632 02:15:15,166 --> 02:15:21,505 SUPPORT THING SUCH AS MULTI-SITE 2633 02:15:21,505 --> 02:15:27,511 CLINICAL TRIALS. 2634 02:15:27,511 --> 02:15:29,613 SOME SITES COULD BE FAR A PART 2635 02:15:29,613 --> 02:15:31,082 AND WHILE IT WOULD PRODUCE A 2636 02:15:31,082 --> 02:15:37,054 QUALITY PRODUCT WE HAD TO ENSURE 2637 02:15:37,054 --> 02:15:42,126 IT GETS TO EACH SITE IN THE SAME 2638 02:15:42,126 --> 02:15:45,663 QUALITY WHICH IS DIFFERENT 2639 02:15:45,663 --> 02:15:52,069 COMPARISON TO CENTERS THAT ARE 2640 02:15:52,069 --> 02:15:55,139 LOCALLY MANUFACTURING JUST FROM 2641 02:15:55,139 --> 02:15:56,340 THEIR CLINICAL TRIAL. 2642 02:15:56,340 --> 02:16:01,512 PUTTING IN PLACE QUALITY SYSTEMS 2643 02:16:01,512 --> 02:16:06,851 AND THINGS LIKE HAVING TO TEST 2644 02:16:06,851 --> 02:16:14,125 THE CRYO FREEZING OF THE CAR T 2645 02:16:14,125 --> 02:16:16,994 CELLS AND HOW WE STANDARDIZE ALL 2646 02:16:16,994 --> 02:16:17,561 THOSE THINGS. 2647 02:16:17,561 --> 02:16:23,000 IT'S BEEN A LOT OF WORK AND 2648 02:16:23,000 --> 02:16:27,772 EFFORT TO BE ABLE TO LEVERAGE 2649 02:16:27,772 --> 02:16:31,876 THE PRODUCT DEVELOPMENT 2650 02:16:31,876 --> 02:16:35,012 EXPERTISE WE HAD AND PUT IT 2651 02:16:35,012 --> 02:16:38,549 TOWARDS ENGINEERING SITE 2652 02:16:38,549 --> 02:16:40,451 THERAPY. 2653 02:16:40,451 --> 02:16:43,487 THIS IS ONE OF THE CLINICAL 2654 02:16:43,487 --> 02:16:48,959 TRIALS WE'RE CURRENTLY 2655 02:16:48,959 --> 02:16:49,260 SUPPORTING. 2656 02:16:49,260 --> 02:16:51,662 WE HAVE MANUFACTURED PRODUCTS 2657 02:16:51,662 --> 02:16:52,997 FOR FOUR DIFFERENT DOSE LEVELS 2658 02:16:52,997 --> 02:17:03,541 AND THIS IS TO GENERATE CAR T 2659 02:17:04,141 --> 02:17:09,013 CELLS DIRECTED TO THE CD33 2660 02:17:09,013 --> 02:17:13,717 ANTIGEN FOR CHILDREN AND YOUNG 2661 02:17:13,717 --> 02:17:16,887 ADULTS WITH ACUTE MYELOID 2662 02:17:16,887 --> 02:17:19,223 LEUKEMIA AND THIS TRIAL BEING 2663 02:17:19,223 --> 02:17:23,394 SPONSORED BY NNDP THE STUDY IS 2664 02:17:23,394 --> 02:17:27,798 BEING LED BY AND YOU CAN SEE WE 2665 02:17:27,798 --> 02:17:28,999 HAVE WITH THE CENTRAL 2666 02:17:28,999 --> 02:17:30,734 MANUFACTURING CAPABILITY, WE'VE 2667 02:17:30,734 --> 02:17:35,806 BEEN ABLE TO MANUFACTURER 2668 02:17:35,806 --> 02:17:38,309 PRODUCTS FOR PATIENTS ACROSS 2669 02:17:38,309 --> 02:17:43,013 SICH DIFFERENT CLINICAL SITES. 2670 02:17:43,013 --> 02:17:46,450 YOU CAN SEE HERE FROM SEATTLE AN 2671 02:17:46,450 --> 02:17:48,052 CHILDREN IN COLORADO TO BOSTON 2672 02:17:48,052 --> 02:17:52,056 AND CHOP AND SOME PATIENTS AT 2673 02:17:52,056 --> 02:17:55,693 NCI ALSO. 2674 02:17:55,693 --> 02:18:05,002 AND THE RESULTS WILL BE 2675 02:18:05,002 --> 02:18:10,307 PRESENTED IN DECEMBER AT THE ASH 2676 02:18:10,307 --> 02:18:20,751 ANNUAL MEETING AND I INVITE YOU 2677 02:18:20,751 --> 02:18:23,020 ALL TO LOOK FOR THE RESULTS 2678 02:18:23,020 --> 02:18:24,788 COMING SOON. 2679 02:18:24,788 --> 02:18:27,992 THIS UNIQUE SITUATION WE'RE IN 2680 02:18:27,992 --> 02:18:31,195 AND GET TO HEAR FROM THE 2681 02:18:31,195 --> 02:18:34,198 CLINICAL P.I.s, THE IMPACT THESE 2682 02:18:34,198 --> 02:18:35,166 PRODUCTS ARE HAVING ON THEIR 2683 02:18:35,166 --> 02:18:45,342 PATIENTS. 2684 02:18:55,219 --> 02:18:56,554 WE'RE ALSO MANUFACTURING CAR T 2685 02:18:56,554 --> 02:19:01,659 CELLS FOR ANOTHER CLINICAL 2686 02:19:01,659 --> 02:19:01,859 TRIAL. 2687 02:19:01,859 --> 02:19:12,403 THE GD2 CAR FOR TRIAL AND DOING 2688 02:19:15,506 --> 02:19:16,073 CENTRALIZED MANUFACTURING FOR 2689 02:19:16,073 --> 02:19:20,077 THIS AND SEVERAL PATIENTS HAVE 2690 02:19:20,077 --> 02:19:23,814 ALSO BEEN DOSED FOR THIS TRIAL 2691 02:19:23,814 --> 02:19:32,089 WANT TO BRING YOU TO THE NEXT 2692 02:19:32,089 --> 02:19:36,060 SLIDE WHERE WITH THE TWO TRIALS 2693 02:19:36,060 --> 02:19:37,061 WE'RE CURRENTLY ACTIVELY 2694 02:19:37,061 --> 02:19:39,863 MANUFACTURING PRODUCT FOR THOSE, 2695 02:19:39,863 --> 02:19:43,767 WE ARE ALSO LEVERAGING OUR 2696 02:19:43,767 --> 02:19:45,369 ABILITY TO DEVELOP PROCESSES AND 2697 02:19:45,369 --> 02:19:47,071 BRING SOME OTHER CANDIDATES TO 2698 02:19:47,071 --> 02:19:53,444 TRIAL. 2699 02:19:53,444 --> 02:19:55,746 HERE'S MANY PROJECTS THAT COME 2700 02:19:55,746 --> 02:19:58,282 TO US THROUGH DIFFERENT 2701 02:19:58,282 --> 02:20:00,918 MECHANISMS BUT PRIMARILY THROUGH 2702 02:20:00,918 --> 02:20:01,418 THE NEXT EXPERIMENTAL 2703 02:20:01,418 --> 02:20:07,191 THERAPEUTICS PROGRAM. 2704 02:20:07,191 --> 02:20:11,061 WE'RE ABLE TO MANUFACTURE AND 2705 02:20:11,061 --> 02:20:12,496 DEVELOP PROCESS TO DEVELOP CAR T 2706 02:20:12,496 --> 02:20:15,766 CELLS OR OTHER PRODUCTS RELATED. 2707 02:20:15,766 --> 02:20:18,902 SO THE VIRUSES THAT ARE USED TO 2708 02:20:18,902 --> 02:20:23,073 DO THE GENETIC ENGINEERING. 2709 02:20:23,073 --> 02:20:25,809 AND I PROMISE TO KEEP THE TEAM 2710 02:20:25,809 --> 02:20:31,348 ON TIME SO I'M GOING TO GO TO 2711 02:20:31,348 --> 02:20:38,389 THE NEXT SLIDE. 2712 02:20:38,389 --> 02:20:41,058 WHAT I WANT TO SAY IS THERE'S 2713 02:20:41,058 --> 02:20:41,925 MANY MANUFACTURING HURDLES 2714 02:20:41,925 --> 02:20:44,061 AHEAD. 2715 02:20:44,061 --> 02:20:45,929 WE'RE TRYING TO ADDRESS THOSE 2716 02:20:45,929 --> 02:20:51,602 AND WHAT WE'RE HOPING TO DO IS 2717 02:20:51,602 --> 02:20:58,342 INCREASE CAPACITY AND ONE OF THE 2718 02:20:58,342 --> 02:21:02,046 WAYS IS BY COMMISSIONING GMP 2719 02:21:02,046 --> 02:21:03,347 MANUFACTURING SUITE FOR THE WORK 2720 02:21:03,347 --> 02:21:06,884 AND WORKING ON OTHER 2721 02:21:06,884 --> 02:21:11,088 MANUFACTURING PLATFORMS AND 2722 02:21:11,088 --> 02:21:11,388 TECHNOLOGY. 2723 02:21:11,388 --> 02:21:12,122 WE EXPECT THERE'S BEEN A LOT OF 2724 02:21:12,122 --> 02:21:15,659 DEVELOPMENT WORK THAT HAS GONE 2725 02:21:15,659 --> 02:21:18,429 INTO MAKING A PROCESS THAT IS 2726 02:21:18,429 --> 02:21:26,804 SCALABLE FOR CRISPR-BASED CELL 2727 02:21:26,804 --> 02:21:27,438 THERAPY PRODUCTS. 2728 02:21:27,438 --> 02:21:30,374 NOT JUST RETROVIRUSES. 2729 02:21:30,374 --> 02:21:32,076 AND ANOTHER TECHNOLOGY THAT 2730 02:21:32,076 --> 02:21:35,512 WE'RE INTRODUCING IS ALSO THE 2731 02:21:35,512 --> 02:21:41,785 IPFCs WHICH MAY BE VALUABLE IN 2732 02:21:41,785 --> 02:21:48,225 MAKING MORE ALLOGENEIC PRODUCTS. 2733 02:21:48,225 --> 02:21:51,395 I'D LIKE TO GO TO THE NEXT SLIDE 2734 02:21:51,395 --> 02:22:01,939 AND TRYING TO END HERE AC WE'RE 2735 02:22:02,740 --> 02:22:06,977 KEEPING THE PATIENTS IN MIND AND 2736 02:22:06,977 --> 02:22:09,546 THIS HAS BEEN WHY WE ARE DOING 2737 02:22:09,546 --> 02:22:12,049 THE WORK WE DO. 2738 02:22:12,049 --> 02:22:15,285 AND THIS SUMMER WE WERE ABLE 2739 02:22:15,285 --> 02:22:20,424 TO -- WE WERE FORTUNATE TO HAVE 2740 02:22:20,424 --> 02:22:22,159 PATIENT FAMILIES VISIT US AND 2741 02:22:22,159 --> 02:22:24,061 ONE OF THE VISITORS WAS ACTUALLY 2742 02:22:24,061 --> 02:22:30,200 A FORMER PEDIATRIC PATIENT THAT 2743 02:22:30,200 --> 02:22:37,207 WAS TREATED ON CD19 CAR T CELL 2744 02:22:37,207 --> 02:22:42,413 TRIAL AND SO WE'RE LOOKING -- 2745 02:22:42,413 --> 02:22:45,015 THIS SOUR GUIDE AND WE'RE HOPING 2746 02:22:45,015 --> 02:22:53,090 TO BRING THE MANUFACTURING 2747 02:22:53,090 --> 02:22:53,624 EXPERTISE TO SOLVE THESE 2748 02:22:53,624 --> 02:22:56,059 PROBLEMS RELATED WITH THE 2749 02:22:56,059 --> 02:23:00,063 MANUFACTURER OF ENGINEERED CAR T 2750 02:23:00,063 --> 02:23:08,572 CELLS. 2751 02:23:08,572 --> 02:23:13,944 THESE ARE SOME OF THE FOLKS WE 2752 02:23:13,944 --> 02:23:20,584 WANT TO ACKNOWLEDGE AND WE HAVE 2753 02:23:20,584 --> 02:23:23,086 THE CONTACT INFORMATION AND IF 2754 02:23:23,086 --> 02:23:27,057 YOU WANT TO KNOW MORE HOW TO 2755 02:23:27,057 --> 02:23:32,062 ACCESS THE RESOURCES AT THE 2756 02:23:32,062 --> 02:23:33,063 FREDERICK LABS FOR MANUFACTURING 2757 02:23:33,063 --> 02:23:35,065 CELLS THE INFORMATION IS MOSTLY 2758 02:23:35,065 --> 02:23:38,202 ONLINE THROUGH THE NCI 2759 02:23:38,202 --> 02:23:39,203 EXPERIMENTAL THERAPEUTICS 2760 02:23:39,203 --> 02:23:41,071 PROGRAM AND THE LINK IS PROVIDED 2761 02:23:41,071 --> 02:23:47,077 HERE OR YOU CAN REQUEST A 2762 02:23:47,077 --> 02:23:52,049 CONSULTATION WITH THE PRODUCT 2763 02:23:52,049 --> 02:23:55,385 DEVELOPMENT STAFF IN DCTD AND 2764 02:23:55,385 --> 02:23:57,020 WILL CONSULT WITH YOU AND TALK 2765 02:23:57,020 --> 02:24:04,027 ABOUT THE MANUFACTURING HURDLES 2766 02:24:04,027 --> 02:24:08,031 OR DEVELOPMENT PROCESS OR 2767 02:24:08,031 --> 02:24:10,901 STRATEGIES THAT YOU ARE FACING 2768 02:24:10,901 --> 02:24:18,242 WITH YOUR OWN SYNTHETIC 2769 02:24:18,242 --> 02:24:18,842 BIOLOGICAL CANDIDATE. 2770 02:24:18,842 --> 02:24:19,510 AND THANK YOU FOR YOUR ATTENTION 2771 02:24:19,510 --> 02:24:21,044 AND IF THERE'S ANY QUESTIONS 2772 02:24:21,044 --> 02:24:25,115 FEEL FREE TO REACH OUT TO ME. 2773 02:24:25,115 --> 02:24:30,120 THANK YOU. 2774 02:24:30,120 --> 02:24:31,688 >> THANK YOU, DR. SOLOMON. 2775 02:24:31,688 --> 02:24:33,524 CAN YOU SAY ONLINE FOR A LITTLE 2776 02:24:33,524 --> 02:24:34,658 BIT AND LET ME SEE IF THERE'S 2777 02:24:34,658 --> 02:24:43,267 ANY QUESTIONS FROM THE AUDIENCE. 2778 02:24:43,267 --> 02:24:43,600 QUESTIONS? 2779 02:24:43,600 --> 02:24:44,368 THANK YOU VERY MUCH. 2780 02:24:44,368 --> 02:24:49,172 MAYBE LET ME JUST ASK ONE QUICK 2781 02:24:49,172 --> 02:24:49,439 QUESTION. 2782 02:24:49,439 --> 02:24:51,475 SO DOES FREDERICK LABORATORY 2783 02:24:51,475 --> 02:24:52,743 ONLY MANUFACTURE MATERIAL THAT 2784 02:24:52,743 --> 02:24:56,947 IS FOR CANCER? 2785 02:24:56,947 --> 02:24:57,948 -- CANCER RESEARCH? 2786 02:24:57,948 --> 02:25:01,518 >> LIMITED FOR CANCER DISEASE OR 2787 02:25:01,518 --> 02:25:02,819 DOES IT ALSO MANUFACTURE 2788 02:25:02,819 --> 02:25:05,455 MATERIALS FOR OTHER DISEASES? 2789 02:25:05,455 --> 02:25:15,933 >> THAT'S A GREAT QUESTION. 2790 02:25:18,001 --> 02:25:21,438 WE'RE PRIMARILY FUNDED BY NCI SO 2791 02:25:21,438 --> 02:25:24,074 MANY OF OUR PRODUCTS ARE FOR 2792 02:25:24,074 --> 02:25:27,077 CANCER INDICATIONS BUT WE DO 2793 02:25:27,077 --> 02:25:30,948 ALSO SUPPORT SOME PRODUCTS FOR 2794 02:25:30,948 --> 02:25:31,915 OTHER INDICATIONS. 2795 02:25:31,915 --> 02:25:39,022 WE HAVE SUPPORTED WORK FOR 2796 02:25:39,022 --> 02:25:40,157 EXTRAMURAL INVESTIGATORS AND 2797 02:25:40,157 --> 02:25:41,458 INTRAMURAL INVESTIGATES FROM 2798 02:25:41,458 --> 02:25:48,131 OTHER INSTITUTES LIKE NYE NAIAD 2799 02:25:48,131 --> 02:25:50,100 AND INFECTIOUS DISEASE AND SO 2800 02:25:50,100 --> 02:25:50,567 MUCH. 2801 02:25:50,567 --> 02:25:52,069 >> THANK YOU VERY MUCH, 2802 02:25:52,069 --> 02:25:54,771 DR. SOLOMON. 2803 02:25:54,771 --> 02:25:58,208 >> THANK YOU FOR STAYING WITH US 2804 02:25:58,208 --> 02:26:00,644 AND BEING PATIENT WITH US. 2805 02:26:00,644 --> 02:26:03,313 SO WE'RE GOING TO TAKE A BREAK 2806 02:26:03,313 --> 02:26:05,115 AND PLEASE COME BACK HERE AT 2807 02:26:05,115 --> 02:26:10,621 2:45 OR OUR THIRD AND FINAL 2808 02:26:10,621 --> 02:26:12,110 PRESENTATION. 2809 02:26:12,110 --> 02:26:17,015 LET'S RESUME THE SESSION. 2810 02:26:17,015 --> 02:26:20,852 WE'LL HAVE OUR THIRD 2811 02:26:20,852 --> 02:26:22,720 PRESENTATION OF THE LAST 2812 02:26:22,720 --> 02:26:22,954 SPEAKER. 2813 02:26:22,954 --> 02:26:28,793 THE SPEAKER IS DR. ARIEL 2814 02:26:28,793 --> 02:26:31,763 WEINBERGER THE CEO AND 2815 02:26:31,763 --> 02:26:34,699 CO-FOUNDER OF AUTO NOM US 2816 02:26:34,699 --> 02:26:36,601 THERAPEUTICS FOCUSSING ON 2817 02:26:36,601 --> 02:26:37,936 ARTIFICIAL IMMUNE SYSTEMS THAT 2818 02:26:37,936 --> 02:26:40,238 WORK AGAINST INFECTIOUS DISEASES 2819 02:26:40,238 --> 02:26:42,407 AND CANCER. 2820 02:26:42,407 --> 02:26:44,309 HE'S GOING TO GIVE US AN UPDATE 2821 02:26:44,309 --> 02:26:54,686 ON SOME OF THEIR WORK. 2822 02:27:43,635 --> 02:27:46,404 >> SORRY, ABOUT THAT, GUYS. 2823 02:27:46,404 --> 02:27:49,507 THANK YOU, CHIAYENG FOR THE 2824 02:27:49,507 --> 02:27:53,044 INTRODUCTION AND TO JEMONT AND 2825 02:27:53,044 --> 02:27:56,180 THE NIBIB TEAM FOR HAVING US. 2826 02:27:56,180 --> 02:28:01,486 I'M ARIEL WEINBERGER THE CEO OF 2827 02:28:01,486 --> 02:28:04,856 AUTONOMOUS THERAPEUTICS. 2828 02:28:04,856 --> 02:28:07,258 I'M HERE WITH TIM NODDEN OUR CSO 2829 02:28:07,258 --> 02:28:12,096 IN THE FRONT YOU'LL SEE HIM IN A 2830 02:28:12,096 --> 02:28:22,507 MOMENT AS THIS LOADS UP. 2831 02:28:42,126 --> 02:28:44,562 HOPEFULLY I CAN MAKE THIS 2832 02:28:44,562 --> 02:28:44,796 HAPPEN. 2833 02:28:44,796 --> 02:28:48,132 I'M ARIEL WEINBERGER THE CEO OF 2834 02:28:48,132 --> 02:28:49,167 AUTONOMOUS THERAPEUTICS AND OUR 2835 02:28:49,167 --> 02:28:51,169 CSO WILL COUPLE FOR QUESTIONS. 2836 02:28:51,169 --> 02:28:53,538 YOU SEE PICTURES OF US ON THE 2837 02:28:53,538 --> 02:28:53,771 SCREEN. 2838 02:28:53,771 --> 02:28:57,675 WE'RE A COMPANY BASED CLOSE TO 2839 02:28:57,675 --> 02:29:01,546 HERE DOWN ROCKVILLE PIKE IN 2840 02:29:01,546 --> 02:29:04,515 ROCKVILLE, MARYLAND. 2841 02:29:04,515 --> 02:29:06,150 TO FOCUS ON THE CORE OF THE 2842 02:29:06,150 --> 02:29:09,354 COMPANY TO BUILD ESSENTIALLY 2843 02:29:09,354 --> 02:29:11,990 NEXT GENERATION RNA AND USE 2844 02:29:11,990 --> 02:29:16,527 SYNTHETIC BIOLOGY TO CONTROL 2845 02:29:16,527 --> 02:29:23,368 WHEN PROTEINS ARE EXPRESSED. 2846 02:29:23,368 --> 02:29:25,770 IT'S USING SYNTHETIC BIOLOGY 2847 02:29:25,770 --> 02:29:26,637 TO -- I'M HAVING TROUBLE WITH 2848 02:29:26,637 --> 02:29:36,381 SLIDES TODAY, GUYS. 2849 02:29:36,381 --> 02:29:46,858 S I APOLOGIZE FOR THE INTRO. 2850 02:29:58,703 --> 02:30:02,640 THESE ARE PEOPLE IN THE COUNTRY 2851 02:30:02,640 --> 02:30:05,710 LOCATED CLOSEBY AND USE ATHLETIC 2852 02:30:05,710 --> 02:30:07,211 BETH WHERE AND WHERE THERAPEUTIC 2853 02:30:07,211 --> 02:30:09,080 PROTEINS ARE EXPRESSED AND THINK 2854 02:30:09,080 --> 02:30:12,950 OF IT AS USING RNA OR NUCLEIC 2855 02:30:12,950 --> 02:30:14,285 ACID TO BUILD PRECISION 2856 02:30:14,285 --> 02:30:15,486 MEDICINES THAT ONLY EXPRESS 2857 02:30:15,486 --> 02:30:17,121 PROTEINS AND ONLY TRANSLATE 2858 02:30:17,121 --> 02:30:19,991 PROTEINS IN DISEASE CELLS WHILE 2859 02:30:19,991 --> 02:30:22,393 AVOIDING CELLS YOU WANT TO SPARE 2860 02:30:22,393 --> 02:30:23,528 FROM EXOGENOUS PROTEIN 2861 02:30:23,528 --> 02:30:23,828 TRANSLATION. 2862 02:30:23,828 --> 02:30:25,663 TO GIVE YOU MOTIVATION AS TO WHY 2863 02:30:25,663 --> 02:30:28,299 YOU'D WANT TO DO THAT IT MAY BE 2864 02:30:28,299 --> 02:30:29,567 OBVIOUS BUT I'LL DO THIS 2865 02:30:29,567 --> 02:30:34,405 NONETHELESS, IF YOU THINK OF THE 2866 02:30:34,405 --> 02:30:38,543 STATE OF THE ART WHERE HE STAND 2867 02:30:38,543 --> 02:30:44,916 WITH NUCLEIC ACID VACCINES OR 2868 02:30:44,916 --> 02:30:47,485 SELF-AMPLIFYING RNAs OR CIRCULAR 2869 02:30:47,485 --> 02:30:49,153 RNAs THEY'RE ESSENTIALLY NOT 2870 02:30:49,153 --> 02:30:51,322 ABLE TO DISCRIMINATE HEALTHY AND 2871 02:30:51,322 --> 02:30:55,126 DISEASED CELLS OR ABLE TO HAVE 2872 02:30:55,126 --> 02:30:56,594 SPECIFIC PROTEIN TRANSLATION IF 2873 02:30:56,594 --> 02:31:00,164 YOU TAKE THE RNAs AND THEY'RE 2874 02:31:00,164 --> 02:31:03,101 ENCAPSULATED IN NANO PARTICLES 2875 02:31:03,101 --> 02:31:05,536 AND DELIVER TO PROTEIN WHAT YOU 2876 02:31:05,536 --> 02:31:11,442 MAY ENCODE IN THE mRNA VACCINE 2877 02:31:11,442 --> 02:31:14,345 WORKS WELL. 2878 02:31:14,345 --> 02:31:15,246 THEY'LL PRODUCE AS MANY CELLS 2879 02:31:15,246 --> 02:31:16,981 YOU MAY WANT TO AVOID AND 2880 02:31:16,981 --> 02:31:20,651 PRETEND YOU WANT TO GET INTO AN 2881 02:31:20,651 --> 02:31:21,319 ANTIGEN PRESENTING CELL BUT 2882 02:31:21,319 --> 02:31:22,720 PERHAPS WANT TO AVOID A NEURON, 2883 02:31:22,720 --> 02:31:23,020 FOR EXAMPLE. 2884 02:31:23,020 --> 02:31:28,926 WHATEVER IT IS YOU WANT TO AVOID 2885 02:31:28,926 --> 02:31:30,661 TENS TO BE THE CASE IN TERMS OF 2886 02:31:30,661 --> 02:31:34,532 THE CELL ENTRY MECHANISM 2887 02:31:34,532 --> 02:31:36,667 TARGETED AS A RESULT OF THAT, 2888 02:31:36,667 --> 02:31:38,636 YOU'RE ESSENTIALLY GOING HAVE 2889 02:31:38,636 --> 02:31:45,476 ANO GENIC PROTEIN WHERE IT COMES 2890 02:31:45,476 --> 02:31:45,810 INTO CONTACT. 2891 02:31:45,810 --> 02:31:51,782 IF I STEP BACK I SAID RNA AND 2892 02:31:51,782 --> 02:31:53,351 mRNA VACCINES ARE TARGETED IN 2893 02:31:53,351 --> 02:31:55,319 TERMS OF DELIVERY AND YOU'RE 2894 02:31:55,319 --> 02:31:56,354 SAYING THAT'S KIND OF A DUMB 2895 02:31:56,354 --> 02:32:00,758 PROBLEM BECAUSE WE KNOW THEY'RE 2896 02:32:00,758 --> 02:32:02,560 SUCCESSFUL OVER THE LAST THREE 2897 02:32:02,560 --> 02:32:04,562 AND A HALF YEARS AND WHY I MATE 2898 02:32:04,562 --> 02:32:08,466 BE A PROBLEM TO CONSIDER IS 2899 02:32:08,466 --> 02:32:10,568 VACCINE HAVE A REAL ADVANTAGE 2900 02:32:10,568 --> 02:32:11,002 OVER THERAPEUTICS. 2901 02:32:11,002 --> 02:32:13,538 DON'T NEED A HIGH DOSE FOR THE 2902 02:32:13,538 --> 02:32:15,439 VACCINE TO BE EFFECTIVE IF 2903 02:32:15,439 --> 02:32:17,108 YOU'RE THINKING ABOUT LIKE TO 2904 02:32:17,108 --> 02:32:18,643 THE COVID VACCINE AS THE 30 TO 2905 02:32:18,643 --> 02:32:22,346 40 MICROGRAMS AND THAT'S ENOUGH 2906 02:32:22,346 --> 02:32:25,416 TO HAVE INCREDIBLE PROTECTIVITY 2907 02:32:25,416 --> 02:32:27,118 AND HAVE THE IMMUNE SYSTEM TO 2908 02:32:27,118 --> 02:32:29,754 ACT AS AN AMPLIFIER. 2909 02:32:29,754 --> 02:32:31,756 WHAT IF YOU WANTED TO DELIVER A 2910 02:32:31,756 --> 02:32:34,592 THERAPEUTIC PROTEIN, HORMONE, 2911 02:32:34,592 --> 02:32:37,328 ENZYME, ENZYME REPLACEMENT 2912 02:32:37,328 --> 02:32:39,363 THERAPY IN IF YOU WANT TO DO 2913 02:32:39,363 --> 02:32:44,669 THAT YOU HAVE TO TREAT EVERY 2914 02:32:44,669 --> 02:32:46,404 CELL. 2915 02:32:46,404 --> 02:32:49,006 AND ON AVERAGE THE DOSE REQUIRED 2916 02:32:49,006 --> 02:32:59,483 FOR mRNA YOU'RE TALKING THE 2917 02:32:59,717 --> 02:33:02,286 MILLIGRAM RANGE. 2918 02:33:02,286 --> 02:33:05,690 AND MANY CLINICAL TRIALS IS A 2919 02:33:05,690 --> 02:33:07,325 CRISPR CAS AND mRNA THAT ENCODES 2920 02:33:07,325 --> 02:33:09,794 A CAS PROTEIN AND HAVE DOSES UP 2921 02:33:09,794 --> 02:33:11,896 TO 75 MILLIGRAMS. 2922 02:33:11,896 --> 02:33:15,399 NOT MICROGRAMS BUT MILLIGRAMS 2923 02:33:15,399 --> 02:33:17,735 AND NOW I GET IN THE PROBLEM OF 2924 02:33:17,735 --> 02:33:21,472 POTENTIALLY YOU COULD HAVE 2925 02:33:21,472 --> 02:33:22,673 PROTECTIVE PROTEINS WHETHER 2926 02:33:22,673 --> 02:33:28,846 HORMONES LIKE INSULIN AND LIFE 2927 02:33:28,846 --> 02:33:33,251 SAVING BUT CAN YOU CONTROL THAT 2928 02:33:33,251 --> 02:33:38,389 AND LIMIT THE OFF TARGET PROTEIN 2929 02:33:38,389 --> 02:33:40,124 EXPRESSION TO LIMIT AND MAXIMIZE 2930 02:33:40,124 --> 02:33:42,193 THE THERAPEUTIC WINDOW? 2931 02:33:42,193 --> 02:33:43,961 THERE'S TWO PRINCIPLED WAYS. 2932 02:33:43,961 --> 02:33:46,897 ONE IS TO LIMIT WHERE THE mRNA 2933 02:33:46,897 --> 02:33:47,932 GOES. 2934 02:33:47,932 --> 02:33:52,837 YOU CAN MAKE BETTER LIPID NANO 2935 02:33:52,837 --> 02:33:55,473 PARTICLES BY WHICH THEY AVOIDED 2936 02:33:55,473 --> 02:33:57,141 OWNER CELLS AND BY CONSTRUCTION 2937 02:33:57,141 --> 02:33:58,643 THE mRNA GETS INTO SUBSET OF 2938 02:33:58,643 --> 02:34:00,945 CELLS AND YOU CAN DO THE MATH IN 2939 02:34:00,945 --> 02:34:03,881 YOUR HEAD AND PROTEIN WILL ONLY 2940 02:34:03,881 --> 02:34:05,883 BE MADE IN THE CELLS RNA GETS 2941 02:34:05,883 --> 02:34:06,083 INTO. 2942 02:34:06,083 --> 02:34:07,718 SEEMS LIKE ONE SOLUTION 2943 02:34:07,718 --> 02:34:10,288 PRESUMING YOU HAVE A CELL 2944 02:34:10,288 --> 02:34:12,690 SURFACE MARKER THAT 2945 02:34:12,690 --> 02:34:13,624 DIFFERENTIATES HEALTHY AND 2946 02:34:13,624 --> 02:34:15,026 TARGET FROM OFF-TARGET. 2947 02:34:15,026 --> 02:34:17,228 IN THE WAY YOU DON'T WANT TO USE 2948 02:34:17,228 --> 02:34:20,765 THE LMP TO DO THE DISCRIMINATORY 2949 02:34:20,765 --> 02:34:22,300 DECISION YOU CAN MAKE THE 2950 02:34:22,300 --> 02:34:24,135 DECISION AND HAVE THE DATE AS IT 2951 02:34:24,135 --> 02:34:25,536 WERE OCCUR LATER IN THE PROCESS. 2952 02:34:25,536 --> 02:34:29,340 YOU CAN HAVE AN LNP LIKE YOUR 2953 02:34:29,340 --> 02:34:32,743 LNP FOR VACCINES GETS INTO EVERY 2954 02:34:32,743 --> 02:34:34,679 CELL NEARLY EQUIVALENTLY AND NO 2955 02:34:34,679 --> 02:34:37,815 TARGET AT THE LEVEL OF ENTRY BUT 2956 02:34:37,815 --> 02:34:39,517 ONCE IT GETS INTO CELLS THE RNA 2957 02:34:39,517 --> 02:34:41,185 IT INJECTS AND DELIVERS IT'S 2958 02:34:41,185 --> 02:34:43,154 SMART AS IT WERE OR AUTONOMOUS 2959 02:34:43,154 --> 02:34:45,990 IN THE SENSE OF BEING ABLE TO 2960 02:34:45,990 --> 02:34:48,225 SENSE THE INTRACELL DEVELOPMENT 2961 02:34:48,225 --> 02:34:51,462 AND DETERMINE OR DECIDE WHETHER 2962 02:34:51,462 --> 02:34:54,231 OR NOT TO MAKE PROTEIN WHETHER 2963 02:34:54,231 --> 02:34:56,667 IT'S A DISEASED OR NOT DISEASED 2964 02:34:56,667 --> 02:34:58,903 CELL AND EITHER WAY YOU CUT IT 2965 02:34:58,903 --> 02:35:00,771 YOU HAVE THE SAME OUTPUT AT THE 2966 02:35:00,771 --> 02:35:02,640 END OF THE DAY IN TERMS OF 2967 02:35:02,640 --> 02:35:04,508 PRINCIPLES IN LIMITING TARGETING 2968 02:35:04,508 --> 02:35:05,743 PROTEIN EXPRESSION TO THE CELLS 2969 02:35:05,743 --> 02:35:08,379 YOU HOPEFULLY WANT TO TARGET 2970 02:35:08,379 --> 02:35:09,780 WHETHER YOU MAKE THE GATE POST 2971 02:35:09,780 --> 02:35:12,616 ENTRY AT THE LEVEL OF 2972 02:35:12,616 --> 02:35:15,152 TRANSLATION VIA RNA IS CALLED 2973 02:35:15,152 --> 02:35:16,854 SMART FOR LACK OF A BETTER TERM 2974 02:35:16,854 --> 02:35:21,525 AND GATE AT THE POINT OF ENTRY 2975 02:35:21,525 --> 02:35:23,461 THE IMPROVED LIPID NANO 2976 02:35:23,461 --> 02:35:23,861 PARTICLE. 2977 02:35:23,861 --> 02:35:28,366 I SET UP THIS DIFFERENT METHOD 2978 02:35:28,366 --> 02:35:30,334 DOING THINGS AND AND WE WON'T DO 2979 02:35:30,334 --> 02:35:32,837 IT AT THE NANO MART CAL AND EEL 2980 02:35:32,837 --> 02:35:36,774 USE WHAT YOU MIGHT SCHAFSHG OF 2981 02:35:36,774 --> 02:35:39,043 AS OFF THE CELL LIPID NANO 2982 02:35:39,043 --> 02:35:41,612 PARTICLE WITH THE VACCINE AND 2983 02:35:41,612 --> 02:35:44,081 WITH THE STANDARD LIPID NANO 2984 02:35:44,081 --> 02:35:45,449 PARTICLE WITH NO CAPABILITY OF 2985 02:35:45,449 --> 02:35:48,786 DISCRIMINATING CELL TYPE WE CAN 2986 02:35:48,786 --> 02:35:49,987 STILL HAVE THE DISCRIMINATION 2987 02:35:49,987 --> 02:35:53,557 OCCUR BY VIRTUE OF A MOLECULE BY 2988 02:35:53,557 --> 02:35:56,327 SMART RNA AND YOU'RE PROBABLY 2989 02:35:56,327 --> 02:35:56,994 WONDERING IF THAT'S POSSIBLE AND 2990 02:35:56,994 --> 02:35:58,162 HOW YOU COULD DO THAT. 2991 02:35:58,162 --> 02:36:01,665 TO GET TO THAT POINT, YOU 2992 02:36:01,665 --> 02:36:03,667 CERTAINLY COULDN'T USE YOUR OFF 2993 02:36:03,667 --> 02:36:07,271 HE SHELF STANDARD RNA TECHNOLOGY 2994 02:36:07,271 --> 02:36:10,274 OR mRNA OR ANOTHER 2995 02:36:10,274 --> 02:36:12,209 SELF-AMPLIFYING RNA. 2996 02:36:12,209 --> 02:36:16,881 THOSE TECHNOLOGIES ARE 2997 02:36:16,881 --> 02:36:18,949 ESSENTIALLY AND HAVE THE SAME 2998 02:36:18,949 --> 02:36:20,451 KIND OF INFORMATION THEY PROVIDE 2999 02:36:20,451 --> 02:36:23,788 THE SAME INFORMATION TO THE 3000 02:36:23,788 --> 02:36:25,189 RIBOSOME WHETHER A CELL IS 3001 02:36:25,189 --> 02:36:26,590 HEALTHY FOR IF IT WERE INFECTED 3002 02:36:26,590 --> 02:36:27,558 WITH A VIRUS. 3003 02:36:27,558 --> 02:36:28,526 THE FIRST HALF OF THE TALK GOING 3004 02:36:28,526 --> 02:36:30,194 FOR THE NEXT 20, 30 MINUTES I'LL 3005 02:36:30,194 --> 02:36:34,165 SHOW THE CASE OF VIRUSES. 3006 02:36:34,165 --> 02:36:38,402 I'M GOING TO WANT TO PRODUCE A 3007 02:36:38,402 --> 02:36:39,603 PROTEIN IN DISEASE CELLS AND 3008 02:36:39,603 --> 02:36:41,105 CELLS INFECTED WITH A TARGETED 3009 02:36:41,105 --> 02:36:46,343 VIRUS AND WANT TO PRODUCE NO 3010 02:36:46,343 --> 02:36:49,814 PROTEIN AND WANT TO BE SILENT 3011 02:36:49,814 --> 02:36:51,449 TRANSLATIONALLY OR LACKING VIRUS 3012 02:36:51,449 --> 02:36:55,019 AND FOR mRNA HEALTHY OR VIRUS 3013 02:36:55,019 --> 02:36:56,253 INFECTED THE mRNA WOULD PROVIDE 3014 02:36:56,253 --> 02:36:57,888 THE SAME AS THE TEMPLATE FOR 3015 02:36:57,888 --> 02:36:58,522 MAKING PROTEIN. 3016 02:36:58,522 --> 02:37:01,625 WHAT IF I CAN MAKE A NEW CLASS 3017 02:37:01,625 --> 02:37:05,396 OF RNA THAT WAS ESSENTIALLY A 3018 02:37:05,396 --> 02:37:09,099 LOCK ENCRYPTED BY ENCRYPTED FROM 3019 02:37:09,099 --> 02:37:11,235 THE RIBOSOME. 3020 02:37:11,235 --> 02:37:14,371 HIDDEN TRANSLATIONALLY AND 3021 02:37:14,371 --> 02:37:15,339 IMMUNOLOGICALLY SO THE SILENCE 3022 02:37:15,339 --> 02:37:17,107 MEANT IN THE ABSENCE OF A 3023 02:37:17,107 --> 02:37:18,642 SPECIFIC INTRACELLULAR TRIGGER 3024 02:37:18,642 --> 02:37:22,112 OR TARGET IN THIS CASE A VIRAL 3025 02:37:22,112 --> 02:37:23,414 INFECTION, THAT ENCRYPTED VIRAL 3026 02:37:23,414 --> 02:37:24,482 INFECTION IS OFF. 3027 02:37:24,482 --> 02:37:27,518 NO PROTEIN'S COMING OUT OF THERE 3028 02:37:27,518 --> 02:37:29,386 BUT IF YOU INFECT THE CELLS YOU 3029 02:37:29,386 --> 02:37:32,623 TREAT WITH THE ENCRYPTED RNA 3030 02:37:32,623 --> 02:37:36,327 WITH A TARGETED VIRUS IT WILL 3031 02:37:36,327 --> 02:37:37,862 ACTIVATE AND PRODUCE LARGE 3032 02:37:37,862 --> 02:37:41,932 AMOUNTS OF WHATEVER PROTEIN YOU 3033 02:37:41,932 --> 02:37:42,166 ENCODE. 3034 02:37:42,166 --> 02:37:45,302 IT'S IMPORTANT TO NOTE I'M AND 3035 02:37:45,302 --> 02:37:46,670 PLUG AND PLAY SYSTEM AND PUT 3036 02:37:46,670 --> 02:37:49,106 WHENEVER PROTEIN YOU WANT INTO 3037 02:37:49,106 --> 02:37:59,617 THE ENCRYPTED RNA CHASIS AND 3038 02:38:02,987 --> 02:38:05,289 I'VE SHOWN A LOT OF CARTOONS AND 3039 02:38:05,289 --> 02:38:10,628 NOT A HECK OF A LOT OF DATA AND 3040 02:38:10,628 --> 02:38:16,066 WE'LL BUILD AN ENCRYPTED RNA AND 3041 02:38:16,066 --> 02:38:19,470 MAKE PROTEIN FOR INFLUENZA NOT 3042 02:38:19,470 --> 02:38:19,703 PROTEIN. 3043 02:38:19,703 --> 02:38:24,241 YOU GET THE ENCRYPTED RNA INTO 3044 02:38:24,241 --> 02:38:26,644 HUMAN LUNG CELLS DIDN'T REALLY 3045 02:38:26,644 --> 02:38:28,646 MATTER AND IN THE ABSENCE OF 3046 02:38:28,646 --> 02:38:29,914 INFLUENZA WE'RE LOOKING AT 3047 02:38:29,914 --> 02:38:31,949 PROTEIN PRODUCTION FROM THE 3048 02:38:31,949 --> 02:38:34,585 ENCRYPTED RNA. 3049 02:38:34,585 --> 02:38:45,095 YOU SEE BASELINE LEVELS, NEG 3050 02:38:45,763 --> 02:38:50,100 LEGIBLE AND YOU DON'T GET 2 OR 3051 02:38:50,100 --> 02:38:51,669 10X TIMES PROTEIN BUT MASSIVE 3052 02:38:51,669 --> 02:38:52,703 AMOUNTS FIVE LOGS HERE AND 3053 02:38:52,703 --> 02:38:56,173 PROBABLY SAYING, WELL, THAT 3054 02:38:56,173 --> 02:38:59,310 DOESN'T PROVE SENSITIVITY TO THE 3055 02:38:59,310 --> 02:39:02,079 CONTEXT OR PRESENCE OF VIRAL 3056 02:39:02,079 --> 02:39:06,283 TARGET DOESN'T PROVE IT'S 3057 02:39:06,283 --> 02:39:09,753 SENSING THE VIRUS PER SE. 3058 02:39:09,753 --> 02:39:13,857 AND THE CELL GETS AGITATED 3059 02:39:13,857 --> 02:39:17,761 PROPRODUCES IMMUNE PROTEINS AND 3060 02:39:17,761 --> 02:39:19,863 THE ENCRYPTED RNA TURNS ON AND 3061 02:39:19,863 --> 02:39:22,900 IF I INFECT IT WITH VIRAL TARGET 3062 02:39:22,900 --> 02:39:25,936 OR PATHOGEN TO TRIGGER AN INNATE 3063 02:39:25,936 --> 02:39:27,638 IMMUNE RESPONSE US MAY BE 3064 02:39:27,638 --> 02:39:30,007 TALKING ABOUT, YOU WON'T HAVE 3065 02:39:30,007 --> 02:39:31,508 THAT ACTIVATION OF THE ENCRYPTED 3066 02:39:31,508 --> 02:39:33,143 RNA AND ONLY TURN ON FOR 3067 02:39:33,143 --> 02:39:35,813 INFLUENZA AND BE DEAD AS A DUCK 3068 02:39:35,813 --> 02:39:39,984 FOR CORONAVIRUS OR IN THIS CASE 3069 02:39:39,984 --> 02:39:41,885 ANY EMCV. 3070 02:39:41,885 --> 02:39:45,689 I'VE GIVEN THE SENSITIVITY AND 3071 02:39:45,689 --> 02:39:47,992 SPECIFICITY HOW MUCH IT TURNS ON 3072 02:39:47,992 --> 02:39:49,760 FOR INFLUENZA BUT WHAT I HAVEN'T 3073 02:39:49,760 --> 02:39:54,298 ANSWERED IS THE DOUBLE ED-EDGED 3074 02:39:54,298 --> 02:40:00,037 SWORD OF THE SPECIFICITY IF IT 3075 02:40:00,037 --> 02:40:01,305 DETECTS AND TRIGGERS WHATEVER 3076 02:40:01,305 --> 02:40:04,174 PROTEIN YOU ENCODE WHAT THE PAY 3077 02:40:04,174 --> 02:40:05,743 LOAD IS YOU'RE PROBABLY SAYING 3078 02:40:05,743 --> 02:40:06,810 VIRUSES MUTATE AND YOU'LL 3079 02:40:06,810 --> 02:40:08,679 ESSENTIALLY HAVE A TARGET NO 3080 02:40:08,679 --> 02:40:14,618 LONGER SENSED AND A USEFUL 3081 02:40:14,618 --> 02:40:16,587 TECHNOLOGY FOR AN RNA VIRUS FOR 3082 02:40:16,587 --> 02:40:18,355 INFLUENZA AND IT'S NOT. 3083 02:40:18,355 --> 02:40:21,191 WE'LL KEEP THE ENCRYPTED VIRUS 3084 02:40:21,191 --> 02:40:26,430 THE SAME BUT START VARYING THE 3085 02:40:26,430 --> 02:40:28,932 VIRUS. 3086 02:40:28,932 --> 02:40:32,569 AND SAME ENCRYPTED RNA AND SAME 3087 02:40:32,569 --> 02:40:34,538 SEQUENCE LOOK WHAT HAPPENS. 3088 02:40:34,538 --> 02:40:37,141 IT TURNS ON. 3089 02:40:37,141 --> 02:40:39,276 NOW YOU HAVE PAN INFLUENZA A AND 3090 02:40:39,276 --> 02:40:43,614 AN EXAMPLE FROM H1N1 AND THE 3091 02:40:43,614 --> 02:40:45,683 BRANCHS OF THE INFLUENZA FAMILY. 3092 02:40:45,683 --> 02:40:47,785 THE IT WORKS WITH INFLUENZA B 3093 02:40:47,785 --> 02:40:50,521 WHICH IS COOL BECAUSE IT GIVES 3094 02:40:50,521 --> 02:40:52,756 THE NOTION YOU MAY HAVE THE 3095 02:40:52,756 --> 02:40:53,557 BEGINNING OF A PAN INFLUENZA 3096 02:40:53,557 --> 02:40:56,060 TECHNOLOGY WHICH IS NOT THE CASE 3097 02:40:56,060 --> 02:40:58,929 FOR STATE OF THE ART VACCINES. 3098 02:40:58,929 --> 02:41:07,604 READ THE BYLINE AT THE BOTTOM. 3099 02:41:07,604 --> 02:41:12,209 IT'S NOT JUST AN OFF AND ON OR 3100 02:41:12,209 --> 02:41:14,011 BINARY EFFECT BUT IF YOU VARY 3101 02:41:14,011 --> 02:41:15,345 THE AMOUNT OF INFLUENZA YOU 3102 02:41:15,345 --> 02:41:17,281 PROVIDE THE TARGET YOU PROVIDE, 3103 02:41:17,281 --> 02:41:20,884 YOU'D SEE THE MONOTONICALLY 3104 02:41:20,884 --> 02:41:21,985 INCREASING AMOUNT OF PROTEIN 3105 02:41:21,985 --> 02:41:24,655 PRODUCTION OF ACTIVATED OF THE 3106 02:41:24,655 --> 02:41:27,558 ENCRYPTED RNA AND THREE 3107 02:41:27,558 --> 02:41:30,594 DIFFERENT ENCRYPTED V1, V2,V3 3108 02:41:30,594 --> 02:41:31,562 AND WHEN DEVELOPED OVER TIME 3109 02:41:31,562 --> 02:41:38,102 THEY GOT BETTER AND YOU CAN SEE 3110 02:41:38,102 --> 02:41:41,805 AND INFLUENZA VIRUS LOW MOIs OF 3111 02:41:41,805 --> 02:41:44,842 1 IN 1,000 CELLS AND NOVEL NEWER 3112 02:41:44,842 --> 02:41:47,511 VERSIONS ARE EXTREMELY 3113 02:41:47,511 --> 02:41:47,811 RESPONSIVE. 3114 02:41:47,811 --> 02:41:50,614 THE SENSOR IS SENSITIVE AND 3115 02:41:50,614 --> 02:41:52,716 ACTIVATES TO HIGH LEVELS AND 3116 02:41:52,716 --> 02:41:54,284 KEEPS INCREASING MONOTONICALLY 3117 02:41:54,284 --> 02:41:56,453 AS YOU INCREASE THE TARGET IN 3118 02:41:56,453 --> 02:41:58,622 THE CELLS FOR THE ENCRYPTED RNA. 3119 02:41:58,622 --> 02:42:02,259 THE OTHER WAY TO THINK OF IT IS 3120 02:42:02,259 --> 02:42:03,360 BECAUSE DIFFERENT INDIVIDUALS 3121 02:42:03,360 --> 02:42:05,829 HAVE DIFFERENT LEVELS OF VIRUS 3122 02:42:05,829 --> 02:42:07,564 AND YOU'LL HAVE PATIENT-SPECIFIC 3123 02:42:07,564 --> 02:42:10,634 DOSES IF YOU WERE TO PUT 3124 02:42:10,634 --> 02:42:13,937 THERAPEUTIC PROTEIN BASED ON THE 3125 02:42:13,937 --> 02:42:14,538 PATIENT-SPECIFIC LEVELS THE 3126 02:42:14,538 --> 02:42:24,915 AMOUNT OF TARGET IN EACH. 3127 02:42:24,915 --> 02:42:26,917 YOU ARE STARTING TO THINK, 3128 02:42:26,917 --> 02:42:29,620 GREAT, I CAN DETECT INFLUENZA 3129 02:42:29,620 --> 02:42:31,188 BUT IS THIS FOR ONE VIRUS. 3130 02:42:31,188 --> 02:42:31,755 TURNS OUT NOT. 3131 02:42:31,755 --> 02:42:35,793 THIS IS RSV AND WE MAKE AN 3132 02:42:35,793 --> 02:42:42,166 ENCRYPTED RNA AND NOW WE TARGET 3133 02:42:42,166 --> 02:42:42,332 RSV. 3134 02:42:42,332 --> 02:42:45,169 AND YOU HAVE THE SAME EFFECT 3135 02:42:45,169 --> 02:42:47,971 ALONG THE X AXIS AND LOOKING AT 3136 02:42:47,971 --> 02:42:54,611 DIFFERENT RSV VARIANTS AND RSV 3137 02:42:54,611 --> 02:43:01,018 As AND Bs AND BASELINE LEVELS OF 3138 02:43:01,018 --> 02:43:02,653 ENCRYPTED PROTEIN LEVEL IN THE 3139 02:43:02,653 --> 02:43:04,488 PRESENCE OF RSV THREE AND FOUR 3140 02:43:04,488 --> 02:43:08,025 LOGS ABOVE BACKGROUND AND SAME 3141 02:43:08,025 --> 02:43:09,726 DYNAMIC FOR INFLUENZA. 3142 02:43:09,726 --> 02:43:11,762 IF YOU USE THE SAME ENCRYPTED 3143 02:43:11,762 --> 02:43:12,930 RNA IT'S OFF. 3144 02:43:12,930 --> 02:43:15,933 IT'S SPECIFIC TO RSV BUT PAN 3145 02:43:15,933 --> 02:43:16,233 RSV. 3146 02:43:16,233 --> 02:43:20,938 GUESS WHAT, YOU CAN DO THE SAME 3147 02:43:20,938 --> 02:43:23,040 FOR SARS COV2 AND SENSE THE 3148 02:43:23,040 --> 02:43:24,308 PATTERN AND MAKE AN VARIANT 3149 02:43:24,308 --> 02:43:29,179 WHETHER THE ALPHA, BETA, DELTA, 3150 02:43:29,179 --> 02:43:31,748 MOUSE-ADAPTED OMICRON AND 3151 02:43:31,748 --> 02:43:34,785 VARIANTS ALONG THE X AXIS AND IF 3152 02:43:34,785 --> 02:43:36,887 YOU TAKE A PROTEIN COMING OUT OF 3153 02:43:36,887 --> 02:43:38,088 THE ENCRYPTED RNA. 3154 02:43:38,088 --> 02:43:40,958 TO REMIND YOU IN CASE I WENT 3155 02:43:40,958 --> 02:43:44,428 QUICKLY, THE Y AXIS SHOWS THE 3156 02:43:44,428 --> 02:43:50,634 ENCODED PROTEIN IN THAT 3157 02:43:50,634 --> 02:43:52,436 ENCRYPTED mRNA CHASIS. 3158 02:43:52,436 --> 02:43:57,341 IT ONLY ACTIVATES IN THE CONTEXT 3159 02:43:57,341 --> 02:43:59,309 OF SARS COV2 IF IT'S ENCRYPTED 3160 02:43:59,309 --> 02:44:04,815 RNA AND DO IT FOR BIO THREATS AS 3161 02:44:04,815 --> 02:44:05,649 WELL. 3162 02:44:05,649 --> 02:44:08,552 SAME GAME BUT CAN TAKE A SINGLE 3163 02:44:08,552 --> 02:44:10,654 ENCRYPTED RNA AND TURN IT ON TO 3164 02:44:10,654 --> 02:44:12,356 HIGH LEVELS IN THE PRESENCE OF 3165 02:44:12,356 --> 02:44:15,292 THE VIRUS AND IN THE ABSENCE 3166 02:44:15,292 --> 02:44:16,994 IT'S SILENT AND OFF. 3167 02:44:16,994 --> 02:44:21,498 I CAN SHOW YOU WE BUILT THESE 3168 02:44:21,498 --> 02:44:22,633 CRYPTED mRNAs FOR A SLEW OF 3169 02:44:22,633 --> 02:44:28,338 VIRUSES. 3170 02:44:28,338 --> 02:44:30,040 AND OTHER VIRUSES HERE. 3171 02:44:30,040 --> 02:44:33,243 WE'VE DONE IT FOR HPV AND A SLEW 3172 02:44:33,243 --> 02:44:36,680 OF VIRUSES WE'VE DONE THIS FOR. 3173 02:44:36,680 --> 02:44:39,616 I WENT QUICKLY BUT WHAT I TRIED 3174 02:44:39,616 --> 02:44:42,286 TO SHOW YOU WE CAN BUILD 3175 02:44:42,286 --> 02:44:46,523 ESSENTIALLY A CENSOR -- SENSOR 3176 02:44:46,523 --> 02:44:48,225 WILL ACTIVATE TO PRODUCE THE 3177 02:44:48,225 --> 02:44:53,597 PROTEIN ENCODED AND THE ABSENCE 3178 02:44:53,597 --> 02:44:54,631 OFF THE TARGET IS 3179 02:44:54,631 --> 02:44:55,899 TRANSLATIONALLY SILENCED BUT 3180 02:44:55,899 --> 02:44:56,800 HAVEN'T SHOWN THERAPEUTIC IMPACT 3181 02:44:56,800 --> 02:44:58,635 OR RELEVANCE TO THE BEGINNING OF 3182 02:44:58,635 --> 02:45:02,639 THE TALK WHICH WAS COULD WE 3183 02:45:02,639 --> 02:45:06,310 BUILD RNA SENSOR ACTUATORS THAT 3184 02:45:06,310 --> 02:45:07,811 DETERMINE WHERE AND WHERE 3185 02:45:07,811 --> 02:45:08,312 THEY'RE EXPRESSED. 3186 02:45:08,312 --> 02:45:09,746 THAT'S THE NEXT PART OF THE 3187 02:45:09,746 --> 02:45:10,047 TALK. 3188 02:45:10,047 --> 02:45:12,582 INSTEAD OF A REPORTER PROTEIN 3189 02:45:12,582 --> 02:45:14,184 AND PUT A THERAPEUTIC PROTEIN 3190 02:45:14,184 --> 02:45:15,686 YOU PROBABLY WANT TO KNOW IF IT 3191 02:45:15,686 --> 02:45:19,089 WILL HAVE ADVOCACY AND WHAT I 3192 02:45:19,089 --> 02:45:20,424 MEAN BY THAT IS WILL IT RESPOND 3193 02:45:20,424 --> 02:45:22,259 TO THE VIRAL TARGET OR WHATEVER 3194 02:45:22,259 --> 02:45:24,728 TARGET YOU PROVIDE IT WITH 3195 02:45:24,728 --> 02:45:27,064 QUICKLY ENOUGH TO PRODUCE ENOUGH 3196 02:45:27,064 --> 02:45:29,666 THERAPEUTIC PROTEIN TO QUASH AN 3197 02:45:29,666 --> 02:45:31,501 ACUTE INFECTION. 3198 02:45:31,501 --> 02:45:34,471 MAKING A LOT OF PROTEIN ISN'T 3199 02:45:34,471 --> 02:45:37,507 EQUIVALENT TO QUASH AN INFECTION 3200 02:45:37,507 --> 02:45:39,042 THERE'S SPEED AND RATE PRESENT 3201 02:45:39,042 --> 02:45:39,910 IN THERAPEUTIC CASE AND LESS 3202 02:45:39,910 --> 02:45:42,279 PRESENT IN THE REPORTER CASE YOU 3203 02:45:42,279 --> 02:45:42,579 SAW. 3204 02:45:42,579 --> 02:45:44,614 FIRST I HAVE TO CHOOSE WHICH 3205 02:45:44,614 --> 02:45:46,616 THERAPEUTIC PROTEIN TO PUT IN. 3206 02:45:46,616 --> 02:45:49,619 I CAN PUT WHATEVER PROTEIN -- 3207 02:45:49,619 --> 02:45:52,589 APOLOGIZE FOR MY FACILITY OF THE 3208 02:45:52,589 --> 02:45:55,692 MIC, PUT ANY PROTEIN YOU WANT 3209 02:45:55,692 --> 02:46:02,532 INTO AN ENCRYPTED CHASSIS AND 3210 02:46:02,532 --> 02:46:06,303 USE THE SAME PROTEIN FOR 3211 02:46:06,303 --> 02:46:09,973 DIFFERENT ENCRYPTED mRNAs BUT 3212 02:46:09,973 --> 02:46:11,074 CHOOSE WHATEVER PROTEIN YOU 3213 02:46:11,074 --> 02:46:11,274 WANT. 3214 02:46:11,274 --> 02:46:14,778 THIS IS NOT RELEVANT TO THE 3215 02:46:14,778 --> 02:46:18,015 ENCRYPTED mRNA CHASSIS AND THIS 3216 02:46:18,015 --> 02:46:20,684 IS A PROTEIN THAT ESSENTIALLY 3217 02:46:20,684 --> 02:46:25,522 SAY HOST-ACTING IMMUNOMODULE TRY 3218 02:46:25,522 --> 02:46:29,793 PROTEIN AND mRNA SO IT'S NOT THE 3219 02:46:29,793 --> 02:46:31,995 FANCY STUFF. 3220 02:46:31,995 --> 02:46:33,630 YOU CAN TAKE THE ENTRIES ALONG 3221 02:46:33,630 --> 02:46:36,233 THE X VIRUS AND VIRUSES AND I'LL 3222 02:46:36,233 --> 02:46:37,667 SHOW ONE EXAMPLE THEY'RE ALL 3223 02:46:37,667 --> 02:46:42,305 BASICALLY THE SAME PATTERN TAKE 3224 02:46:42,305 --> 02:46:44,274 INFLUENZA A AND WHAT THE HEIGHT 3225 02:46:44,274 --> 02:46:46,610 OF THE BAR SHOWS ON THE Y AXIS 3226 02:46:46,610 --> 02:46:49,312 IS ESSENTIALLY THE LEVEL OF 3227 02:46:49,312 --> 02:46:52,115 KNOCK DOWN THAT THE PROTEIN OR 3228 02:46:52,115 --> 02:46:54,918 mRNA WHICH ENCODES THE 3229 02:46:54,918 --> 02:46:56,720 IMMUNOMO 3230 02:46:56,720 --> 02:47:00,323 IMMUNOMO 3231 02:47:00,323 --> 02:47:05,395 IMMUNOMODULATORY PROTEIN MARKS 3232 02:47:05,395 --> 02:47:07,964 AND THE LNP ENCAPSULATE THE PRE 3233 02:47:07,964 --> 02:47:11,134 TEEN AND THE OTHER CULTURE 3234 02:47:11,134 --> 02:47:13,737 TREATED WITH THE GFP OR REPORTER 3235 02:47:13,737 --> 02:47:13,970 PROTEIN. 3236 02:47:13,970 --> 02:47:16,073 I'M CONTROLLING FOR THE 3237 02:47:16,073 --> 02:47:17,274 PRODUCTION PROCESS AND LNP. 3238 02:47:17,274 --> 02:47:20,110 I WANT TO SEE THE EFFECT OF THE 3239 02:47:20,110 --> 02:47:21,244 PROTEIN CONTROLLING AS MUCH AS I 3240 02:47:21,244 --> 02:47:24,347 CAN FOR THE BYSTANDER EFFECTS P 3241 02:47:24,347 --> 02:47:27,617 SYNTHESIS MAY CARRY WITH IT AND 3242 02:47:27,617 --> 02:47:32,756 YOU SEE FOUR OR FIVE LOGS OF 3243 02:47:32,756 --> 02:47:37,327 EFFICACY SOMETIMES WITH THE SAME 3244 02:47:37,327 --> 02:47:38,228 PROTEIN PAY LOAD. 3245 02:47:38,228 --> 02:47:40,197 I'LL TAKE THIS PROTEIN IF YOU 3246 02:47:40,197 --> 02:47:42,632 WANT TO THINK OF IT THAT WAY AND 3247 02:47:42,632 --> 02:47:45,535 ENCRYPT IT SO IT'S NOW GOING TO 3248 02:47:45,535 --> 02:47:47,204 BE BECOME VIRUS SPECIFIC AND YOU 3249 02:47:47,204 --> 02:47:49,673 SAW THE SAME ENCRYPTED RNA 3250 02:47:49,673 --> 02:47:53,577 WORKED FOR EVERY VARIANT OF SAY 3251 02:47:53,577 --> 02:47:58,648 SARS COV2 BUT DIDN'T TURN ON 3252 02:47:58,648 --> 02:48:01,451 WHEN INFLUENZA INFECTED THE 3253 02:48:01,451 --> 02:48:03,987 CELLS AND YOU SEE THE HOST mRNA 3254 02:48:03,987 --> 02:48:11,695 BUT PUTTING IT INTO AN ENCRYPTED 3255 02:48:11,695 --> 02:48:11,928 CHASSIS. 3256 02:48:11,928 --> 02:48:16,299 THIS IS A LONG MOUTHFUL FOR THE 3257 02:48:16,299 --> 02:48:17,601 ENCRYPTED mRNA WITH THE REPORTER 3258 02:48:17,601 --> 02:48:20,971 PROTEIN AND PUT IN THE 3259 02:48:20,971 --> 02:48:23,573 IMMUNOPROTEIN AND SEE IF IT'S 3260 02:48:23,573 --> 02:48:25,308 THERAPEUTIC AND THE EXPERIMENT 3261 02:48:25,308 --> 02:48:30,547 IN CELL CULTURE. 3262 02:48:30,547 --> 02:48:34,784 YOU TAKE CELLS AND TREAT THEM 3263 02:48:34,784 --> 02:48:36,953 WITH AT191 ENCODING THE 3264 02:48:36,953 --> 02:48:41,925 THERAPEUTIC PROTEIN IN BLUE OR 3265 02:48:41,925 --> 02:48:47,497 IN RED THE SAME WITH THE LAN AND 3266 02:48:47,497 --> 02:48:54,337 YOU PUT A NON-THERAPEUTIC A 3267 02:48:54,337 --> 02:49:02,646 REPORTER PROTEIN AND LUCIFERASE 3268 02:49:02,646 --> 02:49:05,815 AND YOU SEE THREE, FOUR LOGS 3269 02:49:05,815 --> 02:49:07,117 WORTH OF EFFICACY. 3270 02:49:07,117 --> 02:49:11,755 IF I DO THE SAME INFLUENZA AND 3271 02:49:11,755 --> 02:49:13,690 DON'T INFECT WITH SARS COV2 I 3272 02:49:13,690 --> 02:49:17,661 GOT NO DIFFERENCE BETWEEN SHAM 3273 02:49:17,661 --> 02:49:18,995 AND REPORTER VERSION AND AGAIN 3274 02:49:18,995 --> 02:49:22,065 THOUGH THE PROTEIN IS PAN VIRAL 3275 02:49:22,065 --> 02:49:24,000 IT'S ONLY GETTING ACTIVATED IN 3276 02:49:24,000 --> 02:49:26,603 THE CONTEXT OF SARS COV2 ON THE 3277 02:49:26,603 --> 02:49:29,973 LEFT AND BECAUSE THE PROTEIN 3278 02:49:29,973 --> 02:49:31,474 DOESN'T GET MADE AND NOT LEAKY 3279 02:49:31,474 --> 02:49:35,078 AND IT'S NOT INHERENTLY 3280 02:49:35,078 --> 02:49:40,183 IMMUNOGENIC IT'S NOT PROTECTIVE 3281 02:49:40,183 --> 02:49:40,750 AGAINST INFLUENZA. 3282 02:49:40,750 --> 02:49:44,020 AND YOU MAKE ENCRYPTED mRNAs AND 3283 02:49:44,020 --> 02:49:47,524 PUT THE SAME PROTEIN INTO THOSE 3284 02:49:47,524 --> 02:49:51,561 CHASSIS AND HERE YOU LOOK AT THE 3285 02:49:51,561 --> 02:49:54,364 ILLUSTRATIVELY AND LOOK AT RSV 3286 02:49:54,364 --> 02:50:00,237 WHICH A RED FLUORESCENT PROTEIN 3287 02:50:00,237 --> 02:50:02,639 EMBEDDED SO IT'S PRODUCING RFP 3288 02:50:02,639 --> 02:50:07,744 AND LOOK FAR LOST YOU SEE 3289 02:50:07,744 --> 02:50:10,580 PROTEIN AND IT'S REPLICATED 3290 02:50:10,580 --> 02:50:12,115 UNHINDERED AND UNTREATED CELLS. 3291 02:50:12,115 --> 02:50:13,450 IF YOU TREAT THEM WITH THE SHAM 3292 02:50:13,450 --> 02:50:15,986 ON THE FAR RIGHT THE ENCRYPTED 3293 02:50:15,986 --> 02:50:18,355 RNA AND NOT ENCODING A 3294 02:50:18,355 --> 02:50:21,424 THERAPEUTIC PROTEIN, NO AFFECT. 3295 02:50:21,424 --> 02:50:23,226 CHASSIS IS NOT A PROBLEM AND IF 3296 02:50:23,226 --> 02:50:26,529 YOU DO THE RIGHT ENCRYPTED RNA 3297 02:50:26,529 --> 02:50:31,701 THAT SENSES RSV BUT PRODUCES A 3298 02:50:31,701 --> 02:50:34,004 THERAPEUTIC PROTEIN CALLED AT225 3299 02:50:34,004 --> 02:50:36,339 AND IF YOU TAKE THE ENCRYPTED 3300 02:50:36,339 --> 02:50:39,809 RNA YOU SEE BASICALLY A BLACK 3301 02:50:39,809 --> 02:50:47,417 BOX IN ABSENCE OF RSV PRODUCED 3302 02:50:47,417 --> 02:50:48,485 RFP AND TO THE KNOCKDOWN IS TWO 3303 02:50:48,485 --> 02:50:56,026 LOG. 3304 02:50:56,026 --> 02:50:58,228 AND THERE'S A SPECIFICITY FOR A 3305 02:50:58,228 --> 02:51:00,363 GIVEN VIRAL FAMILY. 3306 02:51:00,363 --> 02:51:02,632 YOU'RE SAYING TO YOURSELF, WHAT 3307 02:51:02,632 --> 02:51:05,235 IF I WANTED IMMUNITY OR 3308 02:51:05,235 --> 02:51:08,038 PROTECTION AGAINST MULTIPLE 3309 02:51:08,038 --> 02:51:08,938 VIRAL FAMILIES THE WAY IS TO 3310 02:51:08,938 --> 02:51:14,644 BUILD COCKTAILS. 3311 02:51:14,644 --> 02:51:17,447 EACH IS INHERENT INDEPENDENT 3312 02:51:17,447 --> 02:51:20,417 SENSORS AND NO REASON YOU CAN'T 3313 02:51:20,417 --> 02:51:23,386 MAKE COCKTAILS OF INDEPENDENT 3314 02:51:23,386 --> 02:51:23,620 SENSORS. 3315 02:51:23,620 --> 02:51:24,721 HERE'S WHAT HAPPENS IF YOU 3316 02:51:24,721 --> 02:51:26,222 COMBINE THESE AND TREAT CELLS 3317 02:51:26,222 --> 02:51:32,162 WITH BOTH AND LOOK ON THE X 3318 02:51:32,162 --> 02:51:35,732 VIRUS AND NOR SARS OR COV2 OR 3319 02:51:35,732 --> 02:51:40,270 SEE PROTEIN EXPRESSION AND WITH 3320 02:51:40,270 --> 02:51:42,272 RSV ALONE THE RNA SHOOTS UP AND 3321 02:51:42,272 --> 02:51:44,874 THE ENCRYPTED RNA GOES OFF AND 3322 02:51:44,874 --> 02:51:47,877 INFECT WITH SARS COV2 YOU GET 3323 02:51:47,877 --> 02:51:51,314 THE PATTERN. 3324 02:51:51,314 --> 02:51:57,120 AND MAGICALLY IF YOU INFECT WITH 3325 02:51:57,120 --> 02:52:00,056 RSV AND CELLS TREATED YOU GET 3326 02:52:00,056 --> 02:52:02,625 BOTH ENCRYPTED RNAs PLAYING WELL 3327 02:52:02,625 --> 02:52:05,895 TOGETHER AND TURNING ON AND 3328 02:52:05,895 --> 02:52:06,463 RESPONSIVE TO THE MULTIPLE 3329 02:52:06,463 --> 02:52:11,801 CO-INFECTION CASE. 3330 02:52:11,801 --> 02:52:15,705 AND FOR THE EFFICACY AND 3331 02:52:15,705 --> 02:52:16,072 RESPONSIVENESS. 3332 02:52:16,072 --> 02:52:18,208 ONE POINT TO MAKE BEFORE WE GET 3333 02:52:18,208 --> 02:52:19,843 TO THE IN VIVO BECAUSE ENCRYPTED 3334 02:52:19,843 --> 02:52:24,381 RNAs ARE SET UP TO BE 3335 02:52:24,381 --> 02:52:30,387 ESSENTIALLY OFF TRANSLATIONALLY 3336 02:52:30,387 --> 02:52:33,923 SILENT TAILOR-MADE FOR 3337 02:52:33,923 --> 02:52:36,359 PROPHYLAXIS AND ONLY ACTIVATE IN 3338 02:52:36,359 --> 02:52:39,896 THE CONTEXT OF INFECTION AND 3339 02:52:39,896 --> 02:52:45,235 THINK THAT MAY BE DUMB BECAUSE 3340 02:52:45,235 --> 02:52:48,371 RNA IS LABIL AND IT'S NOT GOING 3341 02:52:48,371 --> 02:52:51,741 TO DO A HECK OF A LOT OF GOOD AS 3342 02:52:51,741 --> 02:52:55,178 A PROPHYLACTIC BECAUSE IT WILL 3343 02:52:55,178 --> 02:52:58,648 BE GONE BEFORE YOU'RE INFECTED 3344 02:52:58,648 --> 02:53:06,556 AND COULD WE MODIFY AND WE CAN 3345 02:53:06,556 --> 02:53:10,627 AND USING A TRICK FOR SAY SRNAs 3346 02:53:10,627 --> 02:53:11,628 AND SIMILAR. 3347 02:53:11,628 --> 02:53:17,100 THE EXPERIMENT IS TRIVIAL. 3348 02:53:17,100 --> 02:53:21,337 WITH WE HAVE THE ENCRYPTED RNA 3349 02:53:21,337 --> 02:53:24,407 AND THIS MODIFIED VERSION I'M 3350 02:53:24,407 --> 02:53:34,851 SHOWING IN I GUESS ORANGE. 3351 02:53:35,185 --> 02:53:38,021 IT'S NO ENCRYPTED RNA AND I'LL 3352 02:53:38,021 --> 02:53:39,222 TREAT THEM AT DAY ZERO AND DO 3353 02:53:39,222 --> 02:53:42,125 ANYTHING FOR TWO WEEKS. 3354 02:53:42,125 --> 02:53:45,228 NEVER RETREAT, TWO WEEKS LATER 3355 02:53:45,228 --> 02:53:47,330 I'LL INFECT WITH VIRUS 3356 02:53:47,330 --> 02:53:49,666 SPECIFICALLY RSV ENCRYPTED RNA 3357 02:53:49,666 --> 02:53:50,033 CASE. 3358 02:53:50,033 --> 02:53:53,036 TWO WEEKS LATER YOU INFECT AND 3359 02:53:53,036 --> 02:53:54,838 YOU'RE MEASURING DID THE 3360 02:53:54,838 --> 02:53:56,940 ENCRYPTED RNA STICK AROUND AND 3361 02:53:56,940 --> 02:53:59,008 DID IT STICK AROUND IN A ROBUST 3362 02:53:59,008 --> 02:54:00,376 ENOUGH WAY TO TURN ON IN THE 3363 02:54:00,376 --> 02:54:02,579 CONTEXT OF INFECTION AND 3364 02:54:02,579 --> 02:54:06,382 FUNCTIONALLY IS IT PRESENT AND 3365 02:54:06,382 --> 02:54:07,817 RESPONSIVE TWO WEEKS LATER? 3366 02:54:07,817 --> 02:54:10,653 IT HAS NO PROTEIN PRODUCTION AS 3367 02:54:10,653 --> 02:54:11,354 I SHOULDN'T. 3368 02:54:11,354 --> 02:54:14,457 THE ORIGINAL ONE IS LONG GONE 3369 02:54:14,457 --> 02:54:16,092 AND DOESN'T WORK AT DAY 14 BUT 3370 02:54:16,092 --> 02:54:20,763 DID AT ZERO AND MODIFIED WORKS 3371 02:54:20,763 --> 02:54:23,099 AT DAY 0 AND 14 AND IF THE 3372 02:54:23,099 --> 02:54:24,267 ABSENCE OF THE INFECTION DOESN'T 3373 02:54:24,267 --> 02:54:26,402 PRODUCE PROTEIN YOU INFECT WITH 3374 02:54:26,402 --> 02:54:30,373 RSV WITH THE PLUS AND THE 3375 02:54:30,373 --> 02:54:34,244 MODIFIED RSV CREN ENCRYPTED RNA 3376 02:54:34,244 --> 02:54:36,379 YOU CAN PROPHYLACTICALLY 3377 02:54:36,379 --> 02:54:41,518 ADMINISTER WEEKS IN ADVANCE. 3378 02:54:41,518 --> 02:54:44,187 A 3379 02:54:44,187 --> 02:54:48,157 AND YOU MAY SAY ENCRYPTED mRNA'S 3380 02:54:48,157 --> 02:54:50,627 ARE COOL FOR TWO, THREE WEEKS 3381 02:54:50,627 --> 02:54:52,662 BUT WHAT ABOUT MONTHS? 3382 02:54:52,662 --> 02:55:00,270 YOU HAVE A DNA THAT CAN MAKES ON 3383 02:55:00,270 --> 02:55:04,207 CON STITCHIVE LY EXPRESS THE DN 3384 02:55:04,207 --> 02:55:06,876 AND HAVE A STOP SIGN NO PROTEIN 3385 02:55:06,876 --> 02:55:09,746 UNLESS THE CELLS ARE INCORRECTED 3386 02:55:09,746 --> 02:55:11,881 WITH THE VIRUS AND DO THIS TO 3387 02:55:11,881 --> 02:55:13,182 RESPOND TO INFLUENZA AND WILL 3388 02:55:13,182 --> 02:55:14,651 ONLY EXPRESS PROTEIN IN 3389 02:55:14,651 --> 02:55:15,518 PRINCIPLE IF INFLUENZA IS THERE 3390 02:55:15,518 --> 02:55:18,388 TO ACTIVATE THE ENCRYPTED RNA 3391 02:55:18,388 --> 02:55:24,861 FROM THE DNA. 3392 02:55:24,861 --> 02:55:26,229 AND IT TREATS ONCE AT ZERO. 3393 02:55:26,229 --> 02:55:27,931 THAT'S THE ONLY TIME I TREAT THE 3394 02:55:27,931 --> 02:55:30,934 CELLS AND RUN AT THE CULTURE FOR 3395 02:55:30,934 --> 02:55:35,271 13 WEEKS AND MEASURE PROTEIN AND 3396 02:55:35,271 --> 02:55:37,540 I SEE THE BLEW BOX AT THE ORIGIN 3397 02:55:37,540 --> 02:55:39,509 OF THE Y AXIS WHICH IS GOOD 3398 02:55:39,509 --> 02:55:41,010 BECAUSE I DON'T WANT TO MAKE 3399 02:55:41,010 --> 02:55:51,554 PROTEIN IN THE ABSENCE OF VIRUS. 3400 02:55:51,754 --> 02:56:02,198 I KEEP INFECTING THE ALIQUOT. 3401 02:56:10,540 --> 02:56:12,075 IT'S PERSISTING AND RESPONSIVE 3402 02:56:12,075 --> 02:56:12,375 WEEKS LATER. 3403 02:56:12,375 --> 02:56:15,678 WE DID ONE MORE THING BEFORE I 3404 02:56:15,678 --> 02:56:17,480 GET TO THE COOL IN VIVO DATA. 3405 02:56:17,480 --> 02:56:19,849 WE TOOK THE CELLS AND DID TWO 3406 02:56:19,849 --> 02:56:20,350 PARALLEL STUDIES. 3407 02:56:20,350 --> 02:56:29,192 ONE WITH THE ENCRYPTED RNA AND 3408 02:56:29,192 --> 02:56:32,795 THE PARALLEL CULTURE WAS THE DNA 3409 02:56:32,795 --> 02:56:36,399 ENCODING AND ENCRYPTED DNA WITH 3410 02:56:36,399 --> 02:56:41,270 A REPORTER PROTEIN AND THE DNA 3411 02:56:41,270 --> 02:56:43,172 CASE UNTIL NOW AND INFECT WITH 3412 02:56:43,172 --> 02:56:43,439 INFLUENZA. 3413 02:56:43,439 --> 02:56:44,107 DON'T RETREAT. 3414 02:56:44,107 --> 02:56:49,178 I TREATED EACH CULTURE 13 WEEKS 3415 02:56:49,178 --> 02:56:51,381 AGO AND YOU SEE THE DIFFERENCE. 3416 02:56:51,381 --> 02:56:54,083 NOT ONLY IS IT PAN VARIANT, 3417 02:56:54,083 --> 02:56:58,888 VARIOUS ACTIVATED AND EFFECTIVE 3418 02:56:58,888 --> 02:57:05,962 IT'S PROPHYLACTICALLY INFECTED 3419 02:57:05,962 --> 02:57:06,596 WEEKS IN ADVANCE. 3420 02:57:06,596 --> 02:57:10,600 LET'S MAKE A RUN FOR THE IN VIVO 3421 02:57:10,600 --> 02:57:15,104 DATA. 3422 02:57:15,104 --> 02:57:16,205 SO YOU THINK ABOUT IN VIVO AND 3423 02:57:16,205 --> 02:57:21,844 WANT TO KNOW HOW YOU COULD TEST 3424 02:57:21,844 --> 02:57:26,616 ENCRYP 3425 02:57:26,616 --> 02:57:32,388 ENCRYPTED AND WE BUILT A NOVEL 3426 02:57:32,388 --> 02:57:35,391 LNP WITH THE COMMERCIALLY 3427 02:57:35,391 --> 02:57:40,930 AVAILABLE LNPs SYSTEMICALLY 3428 02:57:40,930 --> 02:57:45,635 DELIVERED WE BUILT AN LNP AND 3429 02:57:45,635 --> 02:57:48,404 RETRACTRY TO THE SHEER FORCE AN 3430 02:57:48,404 --> 02:57:55,812 NEBULIZER WOULD IMPART AND COULD 3431 02:57:55,812 --> 02:57:59,215 AFFECT THE DELIVERY OF THE LNP 3432 02:57:59,215 --> 02:58:01,851 AND BUILT ONE REFRACTORY TO THE 3433 02:58:01,851 --> 02:58:07,356 SHEER FORCE OF AN NEBULIZER AND 3434 02:58:07,356 --> 02:58:11,994 YOU CAN SELF-ADMINISTER. 3435 02:58:11,994 --> 02:58:15,098 ENCRYPTED OR ANY RNA USING THIS 3436 02:58:15,098 --> 02:58:20,636 LNP AS A DELIVERY VECTOR. 3437 02:58:20,636 --> 02:58:22,772 IT'S INHALABLE. 3438 02:58:22,772 --> 02:58:33,316 AND THE LEFT YOU'RE LOOKING AT 3439 02:58:33,983 --> 02:58:36,419 AND IT'S NOT EFFICACY BUT 3440 02:58:36,419 --> 02:58:43,526 ROBUSTNESS IS NOT AFFECTED BY 3441 02:58:43,526 --> 02:58:44,393 NEBULIZATION AND THE 3442 02:58:44,393 --> 02:58:50,500 DIFFERENCE -- TAKE THE NEBULIZED 3443 02:58:50,500 --> 02:58:53,603 LNP AND THE DIFFERS BETWEEN THE 3444 02:58:53,603 --> 02:58:59,709 GREEN AND BLUE CURVE. 3445 02:58:59,709 --> 02:59:03,846 THE GREEN IS THE SHAM AND THE 3446 02:59:03,846 --> 02:59:05,081 DIFFERENCE BETWEEN THOSE IS THE 3447 02:59:05,081 --> 02:59:06,349 DIFFERENCE DUE TO THE PRODUCTION 3448 02:59:06,349 --> 02:59:09,519 OF THE THERAPEUTIC PROTEIN AND 3449 02:59:09,519 --> 02:59:11,387 SAME DIFFERENTIAL BETWEEN GREEN 3450 02:59:11,387 --> 02:59:17,960 AND BLUE WHETHER YOU NEBULIZE 3451 02:59:17,960 --> 02:59:23,800 AND I CAN DO MORE THAN NEBULIZE 3452 02:59:23,800 --> 02:59:26,969 BUT OUT IT FOR AT-HOME STORAGE 3453 02:59:26,969 --> 02:59:29,205 AND PUT IT IN THE FRIDGE AND 3454 02:59:29,205 --> 02:59:34,677 WAITED FOUR MONTHS AND YOU SEE 3455 02:59:34,677 --> 02:59:44,954 THE SAME EFFECT. 3456 02:59:52,695 --> 02:59:56,599 AND WE HAVE LOW-END OFF TARGET 3457 02:59:56,599 --> 02:59:58,634 TISSUES THE LNP ISN'T REACHING 3458 02:59:58,634 --> 02:59:58,835 HERE. 3459 02:59:58,835 --> 03:00:04,740 YOU GET THE POINT. 3460 03:00:04,740 --> 03:00:07,510 YOU CAN LOOK AT -- THIS IS ALL 3461 03:00:07,510 --> 03:00:09,745 LOOKED AT BY A BOARD CERTIFIED 3462 03:00:09,745 --> 03:00:12,415 PATHOLOGIST AND TREATING MICE 3463 03:00:12,415 --> 03:00:16,152 AND ANIMALS WITH THE ENCRYPTED 3464 03:00:16,152 --> 03:00:20,890 LNP AND LOOKING LEFT AT 3465 03:00:20,890 --> 03:00:22,124 ESSENTIALLY MICROGRAPHS BY THE 3466 03:00:22,124 --> 03:00:23,826 BOARD CERTIFIED PATHOLOGIST AND 3467 03:00:23,826 --> 03:00:27,463 LOOK AT RENAL FUNCTION AND 3468 03:00:27,463 --> 03:00:30,132 CLINICAL BLOOD CHEMISTRY. 3469 03:00:30,132 --> 03:00:32,168 EVERYTHING LOOKS GOOD AND LOOK 3470 03:00:32,168 --> 03:00:35,338 AT ANIMALS INFECTED WITH SARS 3471 03:00:35,338 --> 03:00:38,074 COV2 AND LOOK AT THE ACTIVATED 3472 03:00:38,074 --> 03:00:41,577 LNP OR INFECTED ANIMAL THIS 3473 03:00:41,577 --> 03:00:43,779 ENCRYPTED RNA DOESN'T BECOME 3474 03:00:43,779 --> 03:00:45,348 TOXIC POST INHALATION. 3475 03:00:45,348 --> 03:00:46,916 I'M NO EXPERT ON THE MICROGRAPHS 3476 03:00:46,916 --> 03:00:49,352 BUT THE PATHOLOGIST SAYS THEY 3477 03:00:49,352 --> 03:00:50,620 LOOK GOOD. 3478 03:00:50,620 --> 03:00:54,156 WHAT ABOUT EFFICACY? 3479 03:00:54,156 --> 03:00:56,826 YOU TAKE A LETHAL MODEL OF SARS 3480 03:00:56,826 --> 03:00:58,594 COV2 A MOUSE-ADAPTED VIRUS AND 3481 03:00:58,594 --> 03:01:00,696 PASS IT FOR GENERATIONS IN A 3482 03:01:00,696 --> 03:01:00,897 MOUSE. 3483 03:01:00,897 --> 03:01:05,101 IN THIS CASE 30 GENERATIONS AND 3484 03:01:05,101 --> 03:01:07,136 A MODEL SET UP AND PERFORMED AT 3485 03:01:07,136 --> 03:01:09,305 THE STATE OF IOWA AND PASSAGE 3486 03:01:09,305 --> 03:01:11,707 FOR 30 GENERATIONS IS 3487 03:01:11,707 --> 03:01:13,209 ESSENTIALLY HIGHLY LETHAL SUCH 3488 03:01:13,209 --> 03:01:15,211 THAT IN THE ABSENCE OF EFFECTIVE 3489 03:01:15,211 --> 03:01:18,381 THERAPY THE MICE WILL HAVE TO BE 3490 03:01:18,381 --> 03:01:19,849 SACRIFICED OR IT'S ESSENTIALLY 3491 03:01:19,849 --> 03:01:21,817 DEAD, THE MICE THAT IS, IN SEVEN 3492 03:01:21,817 --> 03:01:22,952 TO 10 DAYS. 3493 03:01:22,952 --> 03:01:24,086 SEE THAT WHETHER YOU LOOK AT 3494 03:01:24,086 --> 03:01:26,122 SURVIVAL ON THE RIGHT OR LOOK AT 3495 03:01:26,122 --> 03:01:29,392 BODY WEIGHT ON THE LEFT IN ABOUT 3496 03:01:29,392 --> 03:01:32,962 IF YOU TAKE PBS AND INFECT THE 3497 03:01:32,962 --> 03:01:35,498 ANIMALS WITH AN INTRANASAL 3498 03:01:35,498 --> 03:01:44,740 CHALLENGE OF A 10LD50 AND TREAT 3499 03:01:44,740 --> 03:01:46,776 THEM WIN PBS AND THEY'LL DIE. 3500 03:01:46,776 --> 03:01:50,613 IF YOU TREAT THEM WITH WHAT WE 3501 03:01:50,613 --> 03:01:55,785 CALL AT19 LUC AND THE ACTIVATED 3502 03:01:55,785 --> 03:02:00,423 CHASSIS ENCODING A LUCIFERASE 3503 03:02:00,423 --> 03:02:03,859 THE CHASSIS THE RNA ITSELF THE 3504 03:02:03,859 --> 03:02:06,162 PRODUCTION PROCESS THE LNP NONE 3505 03:02:06,162 --> 03:02:10,967 OF THAT WILL CONJURE OR INFER 3506 03:02:10,967 --> 03:02:13,269 INFECTION AND IF YOU TREAT THEM 3507 03:02:13,269 --> 03:02:17,006 WITH THE BLUE THE A191 THAT 3508 03:02:17,006 --> 03:02:18,407 ENCODES THE THERAPEUTIC PROTEIN 3509 03:02:18,407 --> 03:02:22,912 THE MICE SURVIVE. 3510 03:02:22,912 --> 03:02:27,350 SO IT'S FOR ENCRYPTED RNA AND 3511 03:02:27,350 --> 03:02:29,785 NOTE YOU GIVE AN INHALABLE 3512 03:02:29,785 --> 03:02:33,656 ENOUGH TO PROTECT THE MICE IF 3513 03:02:33,656 --> 03:02:35,858 YOU TREAT 48 HOURS OR TWO DAYS 3514 03:02:35,858 --> 03:02:36,592 PRIOR TO INFECTION. 3515 03:02:36,592 --> 03:02:38,894 THE SAME RESULTS FROM THE LAST 3516 03:02:38,894 --> 03:02:42,498 SLIDE THE SINGLE PROPHYLACTIC 3517 03:02:42,498 --> 03:02:49,105 TREATMENT OR IF YOU TREAT AFTER. 3518 03:02:49,105 --> 03:02:52,541 AND I TREAT THE MICE WITH ONE 3519 03:02:52,541 --> 03:02:57,947 DOSE AND SAME RESULT, IT'S 3520 03:02:57,947 --> 03:03:02,651 PROTECTIVE WHEREAS THE SHAM IS 3521 03:03:02,651 --> 03:03:05,921 NOT PROTECTIVE AND I GUESS THE 3522 03:03:05,921 --> 03:03:07,623 CHASSIS ISN'T PROTECTIVE AND 3523 03:03:07,623 --> 03:03:13,129 NEED TO PRODUCE THE PROTEIN BUT 3524 03:03:13,129 --> 03:03:19,769 YOU COULD BE THINKS IT'S NOT 3525 03:03:19,769 --> 03:03:21,837 ACTIVATING IN VIVO IN TERMS OF 3526 03:03:21,837 --> 03:03:24,173 SARS COV2 INFECTION BUT LEAKING 3527 03:03:24,173 --> 03:03:25,307 THERAPEUTIC PROTEIN AND THAT 3528 03:03:25,307 --> 03:03:27,676 THERAPEUTIC PROTEIN IS 3529 03:03:27,676 --> 03:03:36,986 PROTECTIVE AND CON FEFERS AN IME 3530 03:03:36,986 --> 03:03:45,294 RESPONSE AND AND THAT IS NOT 3531 03:03:45,294 --> 03:03:46,195 PROTECTIVE AGAINST SARS COV2 3532 03:03:46,195 --> 03:03:48,464 WHILE IT IS PROTECTIVE AGAINST 3533 03:03:48,464 --> 03:03:50,633 RSVs AND IF WE SWITCH OUT THE 3534 03:03:50,633 --> 03:03:54,437 SENSOR OR SWITCH OUT THE 3535 03:03:54,437 --> 03:04:04,580 THERAPEUTIC EFFECTER YOU'LL OWE 3536 03:04:04,580 --> 03:04:07,249 ABLATE EFFICACY AND ON THE LEFT 3537 03:04:07,249 --> 03:04:09,385 YOU'RE LOOKING AT SAFETY AND 3538 03:04:09,385 --> 03:04:12,455 LOOKED AT BY A BOARD CERTIFIED 3539 03:04:12,455 --> 03:04:14,390 PATHOLOGIST AND ON THE RIGHT 3540 03:04:14,390 --> 03:04:18,627 VIRAL LOAD KNOCK DOWN WHETHER IN 3541 03:04:18,627 --> 03:04:22,631 THE NAVAL PHARYNX OR OTHER 3542 03:04:22,631 --> 03:04:27,636 TISSUES OF THE HAMSTER MODEL. 3543 03:04:27,636 --> 03:04:32,141 AND ONE WITH NON-VIRAL TARGETS. 3544 03:04:32,141 --> 03:04:34,176 I SHOWED IN VIVO DATA FOR SARS 3545 03:04:34,176 --> 03:04:37,146 COV2 BUT I DIDN'T SHOW YOU COULD 3546 03:04:37,146 --> 03:04:38,981 DO IT FOR OTHER VIRAL TARGETS. 3547 03:04:38,981 --> 03:04:40,983 IN THIS CASE INFLUENZA. 3548 03:04:40,983 --> 03:04:42,618 THE ANALOGOUS SYSTEM. 3549 03:04:42,618 --> 03:04:46,622 IT'S A LETHAL MOUSE MODEL WHERE 3550 03:04:46,622 --> 03:04:53,863 THE INFLUENZA IS A HIGHLY 3551 03:04:53,863 --> 03:04:54,964 VIRULENT INFLUENZA KILL THE MICE 3552 03:04:54,964 --> 03:04:56,465 IN SIX OR EIGHT DAYS IN THE 3553 03:04:56,465 --> 03:05:00,469 SYSTEM BUT IF YOU GIVE IT AT158 3554 03:05:00,469 --> 03:05:02,371 THE INFLUENZA ENCRYPTED RNA THEY 3555 03:05:02,371 --> 03:05:07,710 SURVIVE IF YOU WERE TO GIVE IT 3556 03:05:07,710 --> 03:05:10,045 THE SARS AT191 THE MICE WOULD 3557 03:05:10,045 --> 03:05:10,980 NOT SURVIVE. 3558 03:05:10,980 --> 03:05:12,381 DO IT FOR ANY VIRUS YOU'D LIKE 3559 03:05:12,381 --> 03:05:13,916 IN THE SAME MANNER. 3560 03:05:13,916 --> 03:05:18,354 THIS IS INHALABLE AND WE'VE 3561 03:05:18,354 --> 03:05:22,892 SHOWN YOU CAN TAKE A NOVEL RNA 3562 03:05:22,892 --> 03:05:24,093 ABSENT VIRUS ON TOP AND ABSENCE 3563 03:05:24,093 --> 03:05:27,196 OF A TARGETED VIRUS AND TARGETED 3564 03:05:27,196 --> 03:05:28,297 SEQUENCE OR PROTEIN WHATEVER 3565 03:05:28,297 --> 03:05:29,331 YOU'RE GOING AFTER DOESN'T 3566 03:05:29,331 --> 03:05:32,334 PRODUCE PROTEIN. 3567 03:05:32,334 --> 03:05:35,437 IT'S SILENT AND IMMUNE LOGICALLY 3568 03:05:35,437 --> 03:05:36,906 AND HIGHLY RESPONSIVE AND 3569 03:05:36,906 --> 03:05:38,207 SENSITIVE AND PRODUCES HIGH 3570 03:05:38,207 --> 03:05:42,311 LEVELS OF WHATEVER PROTEIN YOU 3571 03:05:42,311 --> 03:05:44,013 ENCODE NOTABLY THERAPEUTIC 3572 03:05:44,013 --> 03:05:46,015 PROTEINS AND TO WORK TOWARDS THE 3573 03:05:46,015 --> 03:05:47,983 ENDS OF THE TALK YOU'RE PROBABLY 3574 03:05:47,983 --> 03:05:50,486 SAYING THAT'S A COOL STORY BUT 3575 03:05:50,486 --> 03:05:57,293 IS IT RESTRICTED TO VIRUSES. 3576 03:05:57,293 --> 03:05:59,628 AND PRODUCE THERAPEUTIC PROTEINS 3577 03:05:59,628 --> 03:06:04,300 AND WHAT IF I WANTED TO MAKE 3578 03:06:04,300 --> 03:06:05,134 PRECISION CHEMO THERAPIES AND 3579 03:06:05,134 --> 03:06:06,602 HERE I'M LOOKING AT WHAT I 3580 03:06:06,602 --> 03:06:09,138 SHOWED YOU EARLIER BUT NOW WITH 3581 03:06:09,138 --> 03:06:14,476 A NON-VIRAL TARGET. 3582 03:06:14,476 --> 03:06:24,987 IT'S NOT FROM A VIRUS AND YOU 3583 03:06:33,462 --> 03:06:36,865 GET THE SAME EFFECT YOU SAW 3584 03:06:36,865 --> 03:06:38,100 EARLIER AND NOW NOT TO RECOGNIZE 3585 03:06:38,100 --> 03:06:39,602 THE VIRAL TARGET BUT TO 3586 03:06:39,602 --> 03:06:40,803 RECOGNIZE THE NON-VIRAL TARGET. 3587 03:06:40,803 --> 03:06:43,439 YOU CAN DO THIS IN A WAY THAT IS 3588 03:06:43,439 --> 03:06:46,242 ESSENTIALLY NON BINARY BUT 3589 03:06:46,242 --> 03:06:51,113 RESPONSIVE THAT HAS HIGH DYNAMIC 3590 03:06:51,113 --> 03:06:51,313 RANGE. 3591 03:06:51,313 --> 03:06:53,916 HERE I'M KEEPING THE SAME AMOUNT 3592 03:06:53,916 --> 03:06:55,851 OF ENCRYPTED mRNA ACROSS THE 3593 03:06:55,851 --> 03:06:57,319 RIGHT SIDE OF THE PICTURE AND 3594 03:06:57,319 --> 03:06:58,354 THE ENCRYPTED LEVEL DOESN'T 3595 03:06:58,354 --> 03:06:58,587 CHANGE. 3596 03:06:58,587 --> 03:07:00,456 ALL I DO IS CHANGE THE TARGET 3597 03:07:00,456 --> 03:07:03,392 LEVEL AS I INCREASE THE TARGET 3598 03:07:03,392 --> 03:07:04,393 LEVEL YOU SEE THIS MASSIVE 3599 03:07:04,393 --> 03:07:05,127 INCREASE IN THE PROTEIN 3600 03:07:05,127 --> 03:07:08,197 PRODUCTION FROM THE ENCRYPTED 3601 03:07:08,197 --> 03:07:09,665 RNA ESSENTIALLY YOU HAVE MORE 3602 03:07:09,665 --> 03:07:13,902 KEY OR ACTIVATION OR TARGET TO 3603 03:07:13,902 --> 03:07:15,571 ACTIVATE YOUR ENCRYPTED RNA. 3604 03:07:15,571 --> 03:07:17,039 HOPEFULLY I'VE GIVEN YOU A 3605 03:07:17,039 --> 03:07:19,108 PICTURE YOU CAN WORK OUTSIDE OF 3606 03:07:19,108 --> 03:07:19,408 VIRUSES. 3607 03:07:19,408 --> 03:07:21,543 ONE OTHER POINT ABOUT CANCER AND 3608 03:07:21,543 --> 03:07:25,614 SHOW FINAL DATA, CANCERS ARE 3609 03:07:25,614 --> 03:07:29,652 HAVE A SECOND CHALLENGE TO THEM 3610 03:07:29,652 --> 03:07:30,119 P 3611 03:07:30,119 --> 03:07:30,252 . 3612 03:07:30,252 --> 03:07:31,820 ON ONE HAND WE HAVE INTERESTING 3613 03:07:31,820 --> 03:07:33,489 TARGETS TO MAKE A 3614 03:07:33,489 --> 03:07:34,490 CANCER-SPECIFIC mRNA BUT YOU MAY 3615 03:07:34,490 --> 03:07:38,460 WANT TO TARGET MORE THAN ONE 3616 03:07:38,460 --> 03:07:39,528 SPECIFIC MUTATION OR SEQUENCE. 3617 03:07:39,528 --> 03:07:42,031 WHAT I MEAN BY THAT IS CANCERS 3618 03:07:42,031 --> 03:07:44,733 IN GENERAL TIPIFY NOT BY A 3619 03:07:44,733 --> 03:07:46,468 SINGLE MUTATION BUT 3620 03:07:46,468 --> 03:07:47,369 CONSTELLATION OF MULTIPLE 3621 03:07:47,369 --> 03:07:47,670 MUTATIONS. 3622 03:07:47,670 --> 03:07:50,472 THIS IS REAL DATA FROM PATIENTS 3623 03:07:50,472 --> 03:07:53,309 AND A COUPLE PAPERS FROM SCIENCE 3624 03:07:53,309 --> 03:07:56,545 AND NATURE AND BREAST CANCER 3625 03:07:56,545 --> 03:07:58,247 PATIENTS WITH METASTATIC BREAST 3626 03:07:58,247 --> 03:08:01,517 CANCERS IN COMPARISON TO HEALTHY 3627 03:08:01,517 --> 03:08:03,319 TISSUES WHERE YOU SEE LOOK AT 3628 03:08:03,319 --> 03:08:06,288 COLUMN A AND PATIENTS WITH NO 3629 03:08:06,288 --> 03:08:10,859 MUTATIONS IN A RANGE OF 3630 03:08:10,859 --> 03:08:14,763 ONCOGENES WHICH ARE ACTIVATING 3631 03:08:14,763 --> 03:08:17,333 ONCOGENES OR TUMOR SUPPRESSER 3632 03:08:17,333 --> 03:08:20,369 GENE AND LOSS OF MUTATION WOULD 3633 03:08:20,369 --> 03:08:23,772 BE TUMORIGENIC AND IF YOU LOOK 3634 03:08:23,772 --> 03:08:26,642 YOU HAVE NO MUTATIONS IN THE 3635 03:08:26,642 --> 03:08:31,280 HEALTHY TISSUE THAT'S WHAT THE 3636 03:08:31,280 --> 03:08:34,683 ENTRY BOX MEANS AND IF YOU LOOK 3637 03:08:34,683 --> 03:08:36,919 ACROSS SIX DIFFERENT PATIENTS, B 3638 03:08:36,919 --> 03:08:42,524 THROUGH G YOU SEE EACH HAS AT 3639 03:08:42,524 --> 03:08:48,497 LEAST TWO OR THREE THREE 3640 03:08:48,497 --> 03:08:53,569 MUTATIONS AND NOT A SINGLE ONO 3641 03:08:53,569 --> 03:08:55,971 GENIC MUTATION WITH THE 3642 03:08:55,971 --> 03:08:56,338 TRANSFORMATION. 3643 03:08:56,338 --> 03:08:57,906 WHAT I MIGHT BE INTERESTED IN 3644 03:08:57,906 --> 03:09:01,310 DOING IS HAVING ENCRYPTED RNA 3645 03:09:01,310 --> 03:09:02,277 THAT FUNCTIONS LIKE A GATE THAT 3646 03:09:02,277 --> 03:09:06,081 NOT ONLY TURNS ON A SINGLE 3647 03:09:06,081 --> 03:09:09,084 CANCER MUTATION IS PRESENT BUT 3648 03:09:09,084 --> 03:09:11,587 MULTIPLE ONES ARE THERE AND 3649 03:09:11,587 --> 03:09:14,656 UNLOCKING OF MULTIPLE LOCKS AT 3650 03:09:14,656 --> 03:09:18,193 EACH TUMOR MUTATION MIGHT LOCK, 3651 03:09:18,193 --> 03:09:19,728 ABSENCE ALL THOSE BEING THERE 3652 03:09:19,728 --> 03:09:22,598 THE ENCRYPTED mRNA IS OFF AND 3653 03:09:22,598 --> 03:09:23,465 YOU CAN MAKE N GATES. 3654 03:09:23,465 --> 03:09:24,500 HERE'S THE DATA. 3655 03:09:24,500 --> 03:09:30,506 YOU HAVE ANY ENCRYPTED TRAINED 3656 03:09:30,506 --> 03:09:36,145 TO ACTIVATE A FOUR DIFFERENT 3657 03:09:36,145 --> 03:09:37,746 SIGNALS HAVE TO BE PRESENT THE 3658 03:09:37,746 --> 03:09:40,115 COLORED IN ENTRY OF THE TABLE 3659 03:09:40,115 --> 03:09:41,350 MEANS THAT SIGNAL'S PROVIDED TO 3660 03:09:41,350 --> 03:09:43,852 CELLS AND YOU SEE ONLY THE FAR 3661 03:09:43,852 --> 03:09:46,221 RIGHT ONLY THE CASE WHERE I GIVE 3662 03:09:46,221 --> 03:09:48,724 ALL FOUR SIGNALS DOES THE 3663 03:09:48,724 --> 03:09:51,493 ENCRYPTED mRNA TURN ON AND SIX 3664 03:09:51,493 --> 03:09:53,162 COLUMNS, I BELIEVE. 3665 03:09:53,162 --> 03:09:54,596 LOOKS LIKE SIX COLUMNS. 3666 03:09:54,596 --> 03:09:56,765 IN EACH CASE I TREAT THE 3667 03:09:56,765 --> 03:10:01,103 RESPECTIVE CELL CULTURE WITH AN 3668 03:10:01,103 --> 03:10:03,038 ENCRYPTED mRNA AND BASICALLY 3669 03:10:03,038 --> 03:10:05,274 PROVIDE ONE OF FOUR OR ALL FOUR 3670 03:10:05,274 --> 03:10:07,476 SIGNALS BUT ONLY WHEN I PROVIDE 3671 03:10:07,476 --> 03:10:10,746 THE SIGNALS DOES THE mRNA TURN 3672 03:10:10,746 --> 03:10:13,015 ON AND UP TO THREE LOGS ABOVE 3673 03:10:13,015 --> 03:10:15,818 BACKGROUND SO HIGHLY RESPONSIVE 3674 03:10:15,818 --> 03:10:19,221 AND NOW IT'S SPECIFIC BECAUSE 3675 03:10:19,221 --> 03:10:21,990 IT'S AN AND GATE AND ONE THING 3676 03:10:21,990 --> 03:10:25,127 TO HINT YOU TOWARD THE FUTURE WE 3677 03:10:25,127 --> 03:10:27,629 CAN ACTIVATE THE ENCRYPTED RNA 3678 03:10:27,629 --> 03:10:29,465 AND TEST THE EFFICACY AGAINST 3679 03:10:29,465 --> 03:10:30,499 THE TUMOR. 3680 03:10:30,499 --> 03:10:33,802 THIS THE B16F10 MODEL FOR MICE. 3681 03:10:33,802 --> 03:10:34,903 A BLACK 6 MICE. 3682 03:10:34,903 --> 03:10:37,940 IF YOU WANT TO GIVE THEM A 3683 03:10:37,940 --> 03:10:41,109 TUMOR, SOUNDS TERRIBLE BUT WHAT 3684 03:10:41,109 --> 03:10:42,511 YOU TAKE MOUSE CANCER CELLS AND 3685 03:10:42,511 --> 03:10:43,879 IMPLANT THEM INTO MOUSE AND WAIT 3686 03:10:43,879 --> 03:10:46,381 A CERTAIN AMOUNT OF DAYS AND 10 3687 03:10:46,381 --> 03:10:48,317 DAYS AND SUBSEQUENTLY TREAT THEM 3688 03:10:48,317 --> 03:10:53,121 WITH A SHAM OR THE ACTIVATED 3689 03:10:53,121 --> 03:10:54,756 ENCRYPTED GMP RNA AND LOOK AT 3690 03:10:54,756 --> 03:10:56,625 TUMOR VOLUME AT THE GROWTH OF 3691 03:10:56,625 --> 03:11:01,463 THE CANCER AND OF YOU SEE THE 3692 03:11:01,463 --> 03:11:02,631 STATISTICALLY SIGNIFICANT KNOCK 3693 03:11:02,631 --> 03:11:04,399 DOWN IN TUMOR SIZE OR TUMOR 3694 03:11:04,399 --> 03:11:04,633 GROWTH. 3695 03:11:04,633 --> 03:11:08,170 SEE THE EFFICACY HERE. 3696 03:11:08,170 --> 03:11:10,272 I'LL END WITH THAT BECAUSE WE'RE 3697 03:11:10,272 --> 03:11:11,406 COMING TOWARD THE END OF THE 3698 03:11:11,406 --> 03:11:13,742 TALK AND I'VE GIVEN A PICTURE 3699 03:11:13,742 --> 03:11:16,278 HOW TO USE ENCRYPTED mRNA IN 3700 03:11:16,278 --> 03:11:18,514 VIRAL AND NON-VIRAL CONTEXT AND 3701 03:11:18,514 --> 03:11:20,449 HOW TO BUILD CANDIDATES 3702 03:11:20,449 --> 03:11:22,618 RESPONSIVE TO AN ARRAY OF 3703 03:11:22,618 --> 03:11:26,021 VIRUSES IN COMBINATION ENCRYPTED 3704 03:11:26,021 --> 03:11:34,930 mRNA'S ONE WE CALL AT225 AND 3705 03:11:34,930 --> 03:11:36,498 GOING BACK TO THE NATIONAL POINT 3706 03:11:36,498 --> 03:11:38,634 OF THE TALK MORE THAN DEVELOPING 3707 03:11:38,634 --> 03:11:40,235 THE CANDIDATES I'D SAY THE HIGH 3708 03:11:40,235 --> 03:11:43,305 LEVEL GOAL OF THE COMPANY IS TO 3709 03:11:43,305 --> 03:11:45,541 USE RNA IN SYNTHETIC BIOLOGY TO 3710 03:11:45,541 --> 03:11:47,075 CONTROL THE THERAPEUTIC WINDOW 3711 03:11:47,075 --> 03:11:50,579 OF NOVEL BIOLOGICS BY 3712 03:11:50,579 --> 03:11:53,682 CONTROLLING THE CAPACITY OF THE 3713 03:11:53,682 --> 03:11:56,585 PROTEINS THOSE RNAs ENCODE USING 3714 03:11:56,585 --> 03:11:57,753 RNA TO BUILD AUTONOMOUS 3715 03:11:57,753 --> 03:11:58,620 MEDICINES. 3716 03:11:58,620 --> 03:12:08,764 THANKS. 3717 03:12:10,299 --> 03:12:14,603 >> THANK YOU FOR THE TALK. 3718 03:12:14,603 --> 03:12:17,239 IT WAS VERY INTERESTING AND GOOD 3719 03:12:17,239 --> 03:12:17,439 STUFF. 3720 03:12:17,439 --> 03:12:20,008 ONE QUESTION I HAD ABOUT THE 3721 03:12:20,008 --> 03:12:22,010 VIRAL ENCODING RNAs. 3722 03:12:22,010 --> 03:12:27,583 I NEOTICED YOU HAD IT WIN THE 3723 03:12:27,583 --> 03:12:30,185 THERAPEUTIC PROTEIN OR WITH THE 3724 03:12:30,185 --> 03:12:31,153 OPPOSITE VIRUS. 3725 03:12:31,153 --> 03:12:41,597 WHAT ABOUT A CONSITUATIVE 3726 03:12:50,672 --> 03:12:57,346 PROT 3727 03:12:57,346 --> 03:12:57,779 PROTEIN? 3728 03:12:57,779 --> 03:12:58,614 >> EXCELLENT QUESTION. 3729 03:12:58,614 --> 03:12:59,247 WE'RE RIGHT. 3730 03:12:59,247 --> 03:13:01,083 WE HAD ALL THE COLUMNS AND I 3731 03:13:01,083 --> 03:13:02,618 PICKED THE RANDOM COLUMN AND 3732 03:13:02,618 --> 03:13:04,920 SAID THE HEIGHT REFLECT THE 3733 03:13:04,920 --> 03:13:06,521 KNOCK DOWN FROM THE mRNA. 3734 03:13:06,521 --> 03:13:16,898 YOU'RE RIGHT, IF YOU 3735 03:13:27,843 --> 03:13:28,977 CONSTITUATIVE CONTROL AND IF I 3736 03:13:28,977 --> 03:13:30,979 WERE TO ANSWER YOUR QUESTION IF 3737 03:13:30,979 --> 03:13:31,947 YOU'RE ASKING WHAT THE ADVANTAGE 3738 03:13:31,947 --> 03:13:33,715 WOULD BE WHAT I JUST IMPLIED. 3739 03:13:33,715 --> 03:13:43,992 YOU COULD HAVE SAFETY AND HAVE 3740 03:13:43,992 --> 03:13:45,627 PROPHYLACTIVE DELIVERY AND AVOID 3741 03:13:45,627 --> 03:13:48,530 WHERE A VIRUS ISN'T PRESENT. 3742 03:13:48,530 --> 03:13:59,074 DOES THAT ANSWER YOUR QUESTION? 3743 03:14:01,910 --> 03:14:10,385 >> I WAS WONDERING ABOUT THE 3744 03:14:10,385 --> 03:14:11,053 CONSTITUTIVE VIRUS. 3745 03:14:11,053 --> 03:14:14,056 >> THANK YOU FOR THE TALK. 3746 03:14:14,056 --> 03:14:15,857 I HAVE A QUESTION ABOUT THE KEY 3747 03:14:15,857 --> 03:14:17,259 TO YOUR LOCK. 3748 03:14:17,259 --> 03:14:21,563 COULD IT BE A LIPID MOLECULE AS 3749 03:14:21,563 --> 03:14:21,930 WELL? 3750 03:14:21,930 --> 03:14:24,466 I CAN THINK OF A MISSING ENZYME 3751 03:14:24,466 --> 03:14:27,335 WITH THE ACCUMULATION OF A LIPID 3752 03:14:27,335 --> 03:14:31,139 NORMALLY FOUND BUT REACHES TOXIC 3753 03:14:31,139 --> 03:14:31,373 LEVELS. 3754 03:14:31,373 --> 03:14:34,576 COULD THEY BE USED TO ACTIVATE 3755 03:14:34,576 --> 03:14:37,379 THE mRNA BUT IN A TARGETED WAY 3756 03:14:37,379 --> 03:14:39,881 LIKE SOME LIPIDS ARE ONLY 3757 03:14:39,881 --> 03:14:46,121 ACCUMULATING IN OLIGO 3758 03:14:46,121 --> 03:14:50,292 DENDROCYTES OR CERTAIN TISSUES. 3759 03:14:50,292 --> 03:14:52,928 I CAN THINK OF A WAY WE'D BE 3760 03:14:52,928 --> 03:14:54,096 ABLE TO DO THAT. 3761 03:14:54,096 --> 03:14:59,501 >> THE FIRST QUESTION IS 3762 03:14:59,501 --> 03:15:02,070 SOMETHING THAT MAYBE WAS NOT 3763 03:15:02,070 --> 03:15:05,140 MENTIONED IN TERMS OF IT BEING 3764 03:15:05,140 --> 03:15:06,975 PROPRIETARY. 3765 03:15:06,975 --> 03:15:10,512 I WAS WONDERING IF YOU CAN GIVE 3766 03:15:10,512 --> 03:15:11,947 A GENERAL OVERVIEW AS TO HINTS 3767 03:15:11,947 --> 03:15:13,682 OF WHAT THE MECHANISM OF THE 3768 03:15:13,682 --> 03:15:15,884 LOCKS IS BECAUSE I'M ENVISIONING 3769 03:15:15,884 --> 03:15:21,089 SOMETHING ALONG THE LINES OF 3770 03:15:21,089 --> 03:15:23,058 ACTOMERS OR RNAs THAT UNFOLD AND 3771 03:15:23,058 --> 03:15:23,592 GET UNLOCKED WHEN THEY'RE 3772 03:15:23,592 --> 03:15:29,231 EXPOSED TO SOMETHING ELSE. 3773 03:15:29,231 --> 03:15:31,733 I'D BE CURIOUS TOE ANYTHING YOU 3774 03:15:31,733 --> 03:15:33,468 SAY ABOUT THAT AND MY SECOND 3775 03:15:33,468 --> 03:15:35,137 QUESTION IS REGARDING VIRAL 3776 03:15:35,137 --> 03:15:37,239 VECTORS AND OTHER GENE DELIVERY 3777 03:15:37,239 --> 03:15:39,741 MECHANISMS BESIDES LIPOSOMES. 3778 03:15:39,741 --> 03:15:43,145 I'M WONDERING IF YOU EXPLORED 3779 03:15:43,145 --> 03:15:44,713 INVESTIGATIONS INTO COUPLING THE 3780 03:15:44,713 --> 03:15:48,316 RNA LOCKS WITH OTHER VECTORS 3781 03:15:48,316 --> 03:15:49,084 BESIDES MECHANISMS AND IF 3782 03:15:49,084 --> 03:15:50,619 THERE'S ADDITIONAL BENEFITS YOU 3783 03:15:50,619 --> 03:15:51,787 CAN ENVISION FOR THAT? 3784 03:15:51,787 --> 03:15:54,055 >> TO YOUR FIRST QUESTION, YES, 3785 03:15:54,055 --> 03:15:56,525 WE HAVE BEEN OPAQUE ABOUT THE 3786 03:15:56,525 --> 03:15:59,361 MECHANISM ACTION AND NEED TO BE 3787 03:15:59,361 --> 03:16:00,562 OPAQUE A LITTLE BIT LONGER AND 3788 03:16:00,562 --> 03:16:02,464 SEE HOW THEY WORK. 3789 03:16:02,464 --> 03:16:04,533 APOLOGIZE FOR NOT BEING MORE 3790 03:16:04,533 --> 03:16:04,966 FORTHRIGHT. 3791 03:16:04,966 --> 03:16:07,536 SECOND QUESTION, THE KEY THING 3792 03:16:07,536 --> 03:16:12,874 IS ACTUALLY THE RNA ITSELF. 3793 03:16:12,874 --> 03:16:16,011 YOU HAVE ANOTHER WAY TO 3794 03:16:16,011 --> 03:16:17,012 INTRODUCE INTO THE CELL WHETHER 3795 03:16:17,012 --> 03:16:20,682 A VIRAL OR PLASMID OR ANOTHER 3796 03:16:20,682 --> 03:16:22,617 WAY OF PRODUCING mRNA IS 3797 03:16:22,617 --> 03:16:32,594 AMENABLE TO HAVING THE WORK. 3798 03:16:32,594 --> 03:16:34,663 >> THANK YOU VERY MUCH. 3799 03:16:34,663 --> 03:16:42,003 REALLY ENGAGING TALK. 3800 03:16:42,003 --> 03:16:44,039 AND THERAPEUTICS ARE REQUIRED TO 3801 03:16:44,039 --> 03:16:46,341 BE DELIVERED A THOUSAND FOLD 3802 03:16:46,341 --> 03:16:48,243 HIGHER THAN mRNA VACCINES. 3803 03:16:48,243 --> 03:16:50,612 I DID NOT SEE ANY INDICATION IN 3804 03:16:50,612 --> 03:16:52,914 THE PRESENTATION THAT FOLLOWED 3805 03:16:52,914 --> 03:16:55,116 WHICH REFLECT A DECREASE IN THE 3806 03:16:55,116 --> 03:16:57,886 DOSAGE THAT WOULD IMPLY A 3807 03:16:57,886 --> 03:16:59,087 DECREASE SO IF YOU CAN SHED 3808 03:16:59,087 --> 03:16:59,621 LIGHT ON THAT. 3809 03:16:59,621 --> 03:17:02,557 >> THAT'S A FAIR POINT. 3810 03:17:02,557 --> 03:17:04,025 WE'RE STILL WORKING ON THE RANGE 3811 03:17:04,025 --> 03:17:06,361 WHERE ESPECIALLY FOR INFECTIOUS 3812 03:17:06,361 --> 03:17:07,662 DISEASE AND THE DOSES WE'RE 3813 03:17:07,662 --> 03:17:11,166 GIVING ARE ON THE ORDER OF WHAT 3814 03:17:11,166 --> 03:17:14,135 YOU WOULD NEED TO GENERATE AN 3815 03:17:14,135 --> 03:17:16,571 IMMUNE RESPONSE SO WE'RE GIVING 3816 03:17:16,571 --> 03:17:18,073 THE EQUIVALENT OF SOMETHING LIKE 3817 03:17:18,073 --> 03:17:22,444 A FEW HUNDRED MICROGRAMS PER 3818 03:17:22,444 --> 03:17:22,644 DOSE. 3819 03:17:22,644 --> 03:17:23,278 ESPECIALLY BECAUSE WE'RE GOING 3820 03:17:23,278 --> 03:17:26,481 TO A LOCAL AREA WE DON'T NEED 3821 03:17:26,481 --> 03:17:27,816 QUITE AS MUCH AS THE SYSTEMIC 3822 03:17:27,816 --> 03:17:29,718 TREATMENTS WHERE I NEED TO 3823 03:17:29,718 --> 03:17:30,352 PROVIDE ENOUGH TREATMENT FOR THE 3824 03:17:30,352 --> 03:17:34,522 WHOLE CIRCULATION. 3825 03:17:34,522 --> 03:17:36,558 >> IF I UNDERSTAND CORRECTLY YOU 3826 03:17:36,558 --> 03:17:38,059 HAVEN'T REALLY SOLVED THAT 3827 03:17:38,059 --> 03:17:38,627 PROBLEM. 3828 03:17:38,627 --> 03:17:41,062 YOU'RE JUST TARGETING YOUR 3829 03:17:41,062 --> 03:17:42,564 THERAPEUTICS TO A LOCALIZED 3830 03:17:42,564 --> 03:17:45,734 AREA? 3831 03:17:45,734 --> 03:17:50,639 >> I DON'T KNOW IF -- WELL, PART 3832 03:17:50,639 --> 03:17:52,440 OF THE LUTION IS PART IS -- 3833 03:17:52,440 --> 03:17:55,577 >> YOU COULD DO THAT WITH 3834 03:17:55,577 --> 03:17:59,314 REGULAR RNA THERAPEUTICS? 3835 03:17:59,314 --> 03:18:02,617 >> THAT'S ONE POSSIBILITY. 3836 03:18:02,617 --> 03:18:07,022 WE CAN AMPLIFY THE DOSE AND WE 3837 03:18:07,022 --> 03:18:10,859 HAVE AN APPLICATION. 3838 03:18:10,859 --> 03:18:19,267 >> THANK YOU. 3839 03:18:19,267 --> 03:18:22,604 >> WE GET QUITE A BIT OF PROTEIN 3840 03:18:22,604 --> 03:18:29,277 FROM THE CONTEXT OF A TARGET. 3841 03:18:29,277 --> 03:18:30,612 THANKS. 3842 03:18:30,612 --> 03:18:31,980 >> THANK YOU VERY MUCH. 3843 03:18:31,980 --> 03:18:36,584 VERY ENGAGING DISCUSSION. 3844 03:18:36,584 --> 03:18:40,322 THANK YOU EVERYONE STICK AROUND 3845 03:18:40,322 --> 03:18:42,590 FOR THE SESSION AND THANK ALL 3846 03:18:42,590 --> 03:18:44,359 THREE SPEAKERS FOR THEIR 3847 03:18:44,359 --> 03:18:44,993 WONDERFUL PRESENTATIONS. 3848 03:18:44,993 --> 03:18:47,662 NOW IT'S TIME TO GO TO THE 3849 03:18:47,662 --> 03:18:48,029 POSTER SESSIONS. 3850 03:18:48,029 --> 03:18:58,029 ENJOY.