SO WHAT I'D LIKE TO DO IS
WELCOME TO YOU THE FOURTH ANNUAL
SYN BIOMEETING I'M JEMONT CHEN.
I'M GLAD WE'RE ABLE TO HAVE THIS
IN PERSON AND I LOOK FORWARD TO
THE DISCUSSION WE'RE GOING HAVE
ON THE STAGE, AT LUNCH, AT
COFFEE BREAKS FOR THE NEXT TWO
DAYS.
TO START IT'S MY PLEASURE TO
INTRODUCE DR. DAVID T. GEORGE.
HE HAS 25 YEARS AS OF SERVICE AT
THE NATIONAL INSTITUTES OF
HEALTH AND POINTED THE DIRECTOR
FOR NIBIB OVERSEEING PROGRAM
DIVISIONS AND BIO ENGINEERING
AND INFORMATICS TRAINING AND
SMALL BUSINESS.
DR. GEORGE FIRST JOINED NIBIB IN
2002 AND APPOINTED ASSOCIATE
DIRECTOR IN 2015 RESPONSIBLE FOR
THE NIBIB NATIONAL ADVISORY
COUNCIL OFFICE OF GRANTS
MANAGEMENT AND SCIENTIFIC REVIEW
AND COMMITTEE MANAGEMENT
ACTIVITIES.
IT'S MY PLEASURE TO WELCOME
DR. GEORGE TO GIVE US OUR
INTRODUCTORY TALK.
THANK YOU.
>> THANK YOU, JEMONT.
I DIDN'T REALIZE JEMONT WAS
GOING TO DO THAT AND I GUESS I'D
BEEN AROUND AT NIBIB.
AS JEMONT MENTIONED I'M THE
ASSOCIATE DIRECTOR FOR
EXTRAMURAL SCIENCE PROGRAM.
I'M EXCITED TO WELCOME YOU HERE
IN PERSON FOR THE FOURTH ANNUAL,
WE USE THE WORD ANNUAL SLIGHTLY
LIBERALLY WITH COVID MODIFYING
THE EVENT OF THE FOURTH NIH
SYNTHETIC BIOLOGY CONSORTIUM
MEETING SO HAPPY TO HOLD IT IN
PERSON FOR THE FIRST TIME
SCIENCE 2019.
THE FOCUS OF THIS YEAR'S MEETING
IS BIO MANUFACTURING AND
SYNTHETIC BIOLOGY.
A TIMELY TOPIC FOR THE COMMUNITY
GATHERED HERE.
THE SPEAKERS AS YOU SEE HERE ARE
WELL RECOGNIZED FROM THE
SYNTHETIC BIOLOGY COMMUNITY.
THEY REPRESENT A VARIETY OF
RESEARCH AREAS AND TODAY WE'LL
BE DISCUSSING ROLES IN BIO
MANUFACTURING RELEVANT TO
SYNTHETIC BIOLOGY.
THEY'RE ALSO REPRESENTATIVE
EXPERTISE FROM INDUSTRY,
ACADEMIA AND GOVERNMENT.
SO I'D LIKE TO WELCOME THE
INVITED SPEAKERS, THE LIGHTNING
SPEAKERS AND THE POSTER
PRESENTERS TODAY.
SO IN TERMS OF BACKGROUND, THIS
AUDIENCE SURELY DOESN'T NEED AN
INTRODUCTION TO SYNTHETIC
BIOLOGY ESPECIALLY FROM A
NON-SYNTHETIC BIOLOGIST BUT TO
REFLECT ON THE HISTORY OF FIELD.
IN 2010, THERE WAS AN ARTICLE IN
NATURAL A NEWS FEATURE ENTITLED
FIVE HARD TRUTHS FOR SYNTHETIC
BIOLOGY TO BECOME A VIABLE
PROCESS IN DEVELOPING FUTURE
PRODUCTS, TOOLS AND
APPLICATIONS.
SINCE THIS PUBLICATION 13 YEARS
LATER, THE RESEARCH DONE BY YOU
THE SYNTHETIC BIOLOGY COMMUNITY
HAVE ADDRESSED AREAS AND
UNPREDICTABLE CIRCUITRY AND
INCOMPATIBLE PARTS AND
VARIABILITY AND CHRIS VOIGT HAD
AN ARTICLE IN NATURE
COMMUNICATIONS DESCRIBING SIX
SYNTHETIC BIOLOGY-BASED PRODUCTS
AVAILABLE IN 2020, A MERE 10
YEARS AFTER CROIX ARTICLE AND A
BIOLOGICAL RATHER THAN CHEMICAL
NITROGEN FERTILIZER COMPATIBLE
WITH CROPS AND ENVIRONMENTALLY
SAFER THAN CHEMICAL NITROGEN
FERTILIZER AND A DIRECTED
EVOLUTION TREATMENT AND A
SHINING EXAMPLE OF SYNTHETIC
BIOLOGY WITH CAR T CELL
IMMUNOTHERAPY FROM GENETICALLY
MODIFIED T CELLS TO ADDRESS
MALIGNANCY AND THESE SHOWCASE
WHAT SYNTHETIC BIOLOGY CAN
ACCOMPLISH IN THE AREAS OF
AGRICULTURE, FOOD, MATERIALS,
AND MEDICINE.
HAVING SEEN GREAT PROGRESS, WHAT
WILL THE FUTURE HOLD, IF WE HOLD
THIS MEETING IN 2036 IN 13 YEARS
WE'LL SEE A LONGER LIST OF
ACCOMPLISHMENTS WHAT'S AN IDEA
BEING TRANSLATED TO PRODUCTS IN
THE FUTURE.
SO GETTING BACK TO THE THEME OF
THIS MEETING, BIO MANUFACTURING
AND THE REASON IT'S IMPORTANT IS
MANUFACTURING PROCESS IS
CRITICAL AT ALL RESEARCH
PRODUCTION SCALES.
THE TRANSLATION FROM LAB SCALE
MANUFACTURING TO INTERMEDIATE
SCALE TO COMMERCIAL PRODUCTION
IS NOT AN EASY ONE AND THERE'S
CRITICAL CHALLENGE TO OVERCOME.
BIO MANUFACTURING NEEDS TO BE
REPEATABLE AND RELIABLE AND
ACCURATE TO RELY ON SYNTHETIC
BIOLOGY TOOLS AND TECHNIQUES TO
BE TRUSTED STEPS IN THE
MANUFACTURING PROCESS.
IT WAS CALLED OUT ON ADVANCING
BIO TECHNOLOGY AND BIO
MANUFACTURING INNOVATION AND THE
EXECUTIVE ORDER REQUESTED HHS
FOR A REPORT ASSESSING HOW TO
USE BIO MANUFACTURING AND BIO
TECHNOLOGY TO REDUCE THE OVER
ALL BURDEN OF DISEASE AND REDUCE
HEALTH OUTCOMES.
AND IT'S LED BY LOUSA RUSSELL
CONTRIBUTED TO THE OUTLYING FIVE
THEMES AND ACCESSIBLE MONITORING
AND BIO MEDICINE AND CELL-BASED
THERAP , A.I. DRIVEN BIO
PRODUCTION OF THERAPIES AND
ADVANCED TECHNIQUES OF GENE
THERAPY AND OUTLINES BOLD GOALS
UNDER EACH THEME.
THE BIO MANUFACTURING ALSO
COMPLIMENTS THE THEMES THE
CONSORTIUM IS ADDRESSING
CHALLENGES IN THE BIOLOGY FIELD
FOR BIO MEDICAL APPLICATIONS.
HERE LISTS THE PAST CONSORTIUM
MEETING THE 2019 WAS THE
INAUGURAL ONE.
2020 IS WHAT IS NO LONGER ANNUAL
AS MANY KNOW WAS CANCELED DUE TO
COVID.
MOVING THROUGH CANCER
APPLICATIONS, CONTROL THEORY,
THIS YEAR BIO MANUFACTURING AND
NEXT YEAR THE NEXT CRITICAL
CHALLENGE IN SYNTHETIC BIOLOGY.
JUST TO GIVE A BRIEF HISTORY OF
THE SYNTHETIC BIOLOGY
CONSORTIUM.
IT WAS FORMED IN 2018 DUE TO A
GROWING INTEREST AT THE TIME.
IT WASN'T CALLED SYNTHETIC
BIOLOGY AT THE TIME.
AS OF NOW THERE'S 12 I.C.s
PARTICIPATING IN THE CONSORTIUM.
THE NAME TAGS OF THOSE ARE MARK.
FOR THOSE YOU HAVEN'T MET REACH
OUT AND HAVE CONVERSATIONS.
THIS LIST HERE SHOWS HIGHLIGHTS
OF SOME OF THE DIFFERENT
WEBSITES FROM THE CONSORTIUM
MEMBERS ON THE TOP RIGHT AND
NIBIB HAS A LIST OF THE MEMBERS
AND THERE'S EXAMPLES FROM NCI
AND HEART, LUNG AND BLOOD AND
NHTRI.
AND JUST TO GIVE A QUICK
OVERVIEW OF THE FUNDING ACTIVITY
OF THE CONSORTIUM ITSELF AND I
WANT TO SAY THIS DOESN'T
REPRESENT 100% OF THE FUNDING AT
NIH BUT THE SPECIFIC INITIATIVES
THE CONSORTIUM MEMBERS HAVE BEEN
WORKING ON.
THIS IS THE TIP OF THE ICEBERG
BUT SOMETHING WE CAN REPORT WITH
PUBLIC DATA AT THE MOMENT.
STARTING WITH 2017 THEY ISSUED
THE FIRST PROGRAM ANNOUNCEMENT
AND STARTED FUNDING IN 2018.
THERE'S A LOT OF MINUTIA IN HERE
SO TAKE IT AS A RESOURCE BUT THE
KEY POINT HERE IS THAT THERE WAS
A PROGRAM ANNOUNCEMENT AND THEN
IT BECAME NOTICE OF SPECIAL
INTEREST WHICH IS A DIFFERENT
WAY THAT NIH DEVELOPED AND
SUPPOSED TO BE EQUIVALENT TO A
PROGRAM ANNOUNCE
THE AND INITIATIVES THAT EXPRESS
A CONTINUOUS INTEREST ON PART OF
THE CONSORTIA MEMBERS ON
SYNTHETIC BIOLOGY AND THE
RESULTING AWARDS FROM IT IN
MILLIONS OF DOLLARS.
THERE WAS AN INITIATIVE WITH NCI
AND NIBIB THAT HAD A SINGLE DUE
DATE AND THIS IS SHOWN HERE.
SO YOU CAN SEE THERE'S BEEN A
GROWING INTEREST IN FUNDING
APPLICATIONS IN SYNTHETIC
BIOLOGY AREA.
AND THIS SHOWS THE AWARDS BY
INSTITUTE.
IT LOOKS LIKE MY LABELS HAVE
DISAPPEARED.
THIS UNDERWRITE IS NIBIB AND
THIS IS NCI.
THERE'S CUSTING AND PASTING --
CUTTING AND PASTING FAILURE ON
MY PART.
AND EARLY ON THERE WERE THREE I
THINK INSTITUTES WERE INVOLVED
INITIALLY AND NOW THE MOST
RECENT EXPRESSIONS OF INTEREST
INCLUDE EIGHT INSTITUTES.
A GROWING NUMBER OF PARTICIPANTS
AS THE AWARDS HAVE GROWN AND
THIS COMES FROM THE INITIATIVE.
THOSE FAMILIAR WITH RCDC CODING
THE WAY WE PUBLICLY REPORT
THERE'S NOT A SYNTHETIC BIOLOGY
CODE SO IT'S DIFFICULT TO TEASE
OUT.
YOU CAN REACH OUT TO THE
INSTITUTES REPRESENTED HERE TO
GET AN IDEA AT A HIGHER LEVEL
WHAT MAY THEY BE FUNDING BUT
THIS IS FOCUSSED ON THE ACTIVES
OF THE CONSORTIA ITSELF.
HERE'S A KEY WORD SNAPSHOT OF
THE WORK SUPPORTED.
IT'S NO SURPRISED TO MANY IN THE
ROOM WITH THE COURT TERMS AND
GENETIC PROGRAMMING, DIRECTED
EVOLUTION, T CELLS, LIVING CELLS
AND DNA AND THE SUBORDINATE
EMPHASIS WHICH COVER A WIDE
RANGE OF DISEASES AND
APPROACHES.
THEN FINALLY LOOKING AT SOME
RECENT AND FUTURE ACTIVITIES.
I HAD MENTIONED THE NOTICE OF
SPECIAL INTEREST THAT WAS LISTED
ON THE BOTTOM OF THE COMPART.
IT WAS RE-ISSUED CONTINUED TO
STATE THE CONSORTIUM'S INTEREST
AND THERE'S EIGHT INSTITUTES ON
IT.
CALLING OUT TOOLS AND
TECHNOLOGIES TO CONTROL
REPROGRAMMING, APPLYING
SYNTHETIC BIOLOGY TO DEVELOPMENT
OF BIOLOGY AND INCREASING
FUNDAMENTAL UNDERSTANDING AND
CONCEPTS AND GAINING FUNDAMENTAL
KNOWLEDGE THROUGH APPLICATION OF
BIOLOGICAL APPROACHES.
IF YOU HAVE QUESTIONS REACH OUT
TO THE PROGRAM DIRECTORS IN THE
NOTICE AND BRING PROJECTS
RELEVANT TO THE MISSION OF THE
INSTITUTE PARTICIPATING ON THE
INITIATIVES.
RECENTLY THE NIBIB AND NIA HAD A
SYNTHETIC BIOLOGY WORKSHOP TO
PROMOTE THE AGING RESEARCHERS
AND IT'S LIKE SPEED DATING WHERE
THERE WERE QUICK TALKS ON WHAT
THEY'RE DOING RESEARCH ON AND
THEN THEY GOT TOGETHER IN
BREAKOUT SESSIONS.
LATER THIS YEAR OR EARLY NEXT
YEAR THERE'LL BE A REPORT
AVAILABLE ON THE WEBSITE TO
DISCUSS THE OUTCOME AND I THINK
JEMONT IF I RECALL, THERE'S A
VIDEOCAST RECORDING THAT WILL BE
AVAILABLE AS WELL, YEAH.
THANK YOU.
IN THE PLANNING STAGES RIGHT NOW
IS ANTICIPATED FOR FALL OF 2024
AN NHLBI, NIBIB TEAMING UP ON
SYNTHETIC BIOLOGY TO MATCH THE
TOOL BUILDERS TO THE TOOL USERS.
SIMILAR TO THE THEORY OF WHAT
WAS DONE WITH THE NIA TO BRING
THE USERS AND DEVELOPERS
TOGETHER TO DEVELOP THE
PRODUCTS.
SO WITH THAT I'LL END MY
WELCOMING REMARKS AND REALLY
EXCITED WE'RE BEING ABLE TO HOLD
THIS MEETING IN PERSON.
I WANT TO DRAW YOUR ATTENTION TO
THE TENTATIVE PLAN FOR NEXT YEAR
WHICH WILL BE ABOUT THIS TIME IN
2024.
THANK YOU VERY MUCH AGAIN FOR
ATTENDING AND HOPE YOU HAVE A
PRODUCTIVE MEETING TODAY AND
TOMORROW.
PLEASE ENJOY DISCUSSING WITH
YOUR COLLEAGUES, MEET SOME NEW
PEOPLE WHO MAYBE YOU HAVEN'T MET
YET.
IF YOU HAVE QUESTIONS ABOUT THE
WORKSHOP, CONTACT JEMONT OR
NICOLE OR OUR WORKSHOP
CONTRACTOR OF STRATEGIC RESULTS
AND THANK YOU TO THE NIH BIOLOGY
CONSORTIA MEMBERS AND OUR
CONTRACTORS TO DEVELOP THE
WORKSHOP AND NIH FOUNDATION FOR
THE ADVANCED EDUCATION IN THE
SCIENCES FOR THE COFFEE BREAKS.
THANK YOU, EVERYONE AND WELCOME
AND HAVE A FANTASTIC MEETING.
THANK YOU.
SO TODAY I'M GOING TO BE
DISCUSSING MY RESEARCH ON
ESSENTIALLY A VERY NEW TYPE OF
TECHNOLOGY AND AT THIS POINT
CURRENTLY A WORK IN PROGRESS BUT
SOMETHING THAT I'M VERY EXCITED
ABOUT I'M GOING TO TALK ABOUT
THREE DIFFERENT GENE THERAPY
VEHICLES I'M IN THE STAGES OF
DEVELOPING ON REALLY I'VE
ENGINEERED THESE AND NOW IN THE
PROCESS OF TESTING THEM.
SO I'M GOING TO BE MAINLY
FOCUSSING TODAY ON THE
ENGINEERING PART, THE DESIGN AND
BUILD PART SINCE THAT'S WHERE I
HAVE THE MOST INTERESTING DATA
SO FAR BUT REST ASSURED THAT I
AM WELL ON MY WAY TO DEVELOPING
CELL BASED IN VITRO ASSAYS AND
HOPE TO SCALE UP TO IN VIVO
ASSAYS IN THE COMING YEARS.
SO MOLECULAR GLUE WAS TITLED AND
HOW DOES IT DESIGN THE NOVEL
GENE THERAPY SYSTEMS?
WHAT I'M USING IS THE SPAY
TAG-SPY CATCHER SYSTEM
ENGINEERED PEPTIDES WHICH REACT
IN A HIGHLY SPECIFIC AND
EFFICIENT FASHION TO FORM A
COVALENT PEPTIDE WITH EACH OTHER
ALLOWING FOR THE LINKAGE OF
PROTEINS AND ALLOWS FOR
ESSENTIALLY ANYTHING TO BE STUCK
TOGETHER IN THE FASHION THAT
ESSENTIALLY YOU CAN MIX THEM AND
THEY'LL JUST LINK WHICH IS
AMAZING.
TO START I'M GOING TO TALK ABOUT
THE FIRST GENE DELIVERY SYSTEM
THAT I AM NOT CHRONOLOGICALLY
FIRST BUT THE FIRST IS CALLED
VAULT AAV.
AAVs ARE A LEADING GENE THERAPY
DELIVERY SYSTEM.
I'M SURE MANY ARE AWARE.
HOWEVER, THERE IS A MAJOR
PROBLEM WITH AAVs IN THAT 30% TO
60% OF PATIENTS ALREADY HAVE
PRE-EXISTING ANTIBODIES WHICH
MAKE THEM OFTEN TIMES INELIGIBLE
FOR TREATMENT OR REQUIRE VERY
COMPLICATED INTERVENTIONS TO
MITIGATE THIS ISSUE SUCH AS
REMOVING PARTS OF THEIR PLASMA
AND SO ON AND SO FORTH.
AND THEY HAVE POTENTIAL AND
CLINICALLY APPROVED FOR FIVE FDA
APPROVED THERAPIES NOW IF I
RECALL CORRECTLY.
AVE AVE
AAVs ARE AWESOME BUT THESE ARE
EXPRESSED IN MOST CELLS
INCLUDING HUMAN CELLS AND
THEY'LL PACK DURING A PEPTIDE
CALLED INT AND PHAGOCYTES AND
AAVs HAVE A BUILT IN MECHANISM
FOR ESCAPING ENDOSOME SINCE
THEY'RE A VIRUS USING THEIR
LIPASE.
THIS IS WHAT I PLAN TO DO
HOPEFULLY IN THE NEXT FEW WEEKS,
ESSENTIALLY A VAULT WHICH HAS
PACKAGED AN AAV WILL BE PACKAGED
AND ESCAPE AND CIRCUMVENT THE
PRESENCE OF ANY ANTIBODIES WHICH
MAY BE PRESENT IN THE SOLUTION.
EEL TALK MORE ABOUT THE ASSAY
I'M WORKING ON FOR THAT DID DEF
YOU SEE SOME PACKAGED HERE AND
HERE, ETCETERA AND THERE'S A
CONTROL WHERE THERE'S NO
PACKAGING BECAUSE I DIDN'T HAVE
THE I.N.T. PEPTIDE AND WHERE THE
MOLECULAR GLUE COMES IN IT HAS A
SPY TAG ON THE PROTEIN AND THE
SPY CATCHER IS FUSED TO THE
I.N.T. PEPTIDE AND THIS PRODUCES
AAV WITH I.N.T. AND MIX IT WITH
THE VAULT AND OVERNIGHT YOU GET
THE PACKAGING WHICH IS GREAT.
YOU SEE NICELY PACKAGED AAVs
INSIDE THE JAR LIKE VAULTS AND
SEE HOW THIS CAN PROTECT THEM
AND AS I MENTIONED I'M NOW
DEVELOPING THIS ASSAY WHERE I'M
USING ANTI-AAV ANTIBODIES AND
I'M INTENDING TO HOPEFULLY LIKE
I SAID IN THE NEXT FEW WEEKS GET
THE DATA IT SHOW THIS PROCESS
WORKING AND HAVING EFFICACY.
ALL RIGHT.
SO I'M GOING TO MOVE ON TO THE
NEXT SYSTEM I'M DEVELOPING NOW.
IT'S CALLED ADD AAV AND THIS IS
CHRONOLOGICALLY THE FIRST I
WORKED ON AND THIS IS ANOTHER
GREAT VIRAL VECTOR IS
ADENOVIRUS.
I WON'T GO IN THE BENEFITS AND
DRAWBACKS RIGHT NOW BUT YOU CAN
TALK TO ME LATER IF YOU'D LIKE.
THEY BOTH HAVE POTENTIAL FOR
FUTURE CRISPR KAS APPLICATIONS
WHICH IS EXCITING BUT WHAT IF WE
CAN COMBINE THESE VEHICLES?
LINKING THEM TO THE ADENO
SURFACE MITIGATING DRAWBACKS AND
ENABLING COMPLEX MULTIGENIC
DELIVERY TO THE SAME CELL IN A
HIGHLY EFFICIENT FASHION.
AND I HAVE MADE GENETIC CAPSID
MODIFICATIONS IN COLLABORATION
WITH OTHER FOLKS IN MY LAB AND
COLLABORATORS AND IN EXTERNAL
LAB AT BAYLOR UNIVERSITY.
WE WERE ABLE TO ASSEMBLE
ESSENTIALLY ADENOVIRUS WITH
HEXON SPY TAG THE 720 COPY IN
THE CAPSID AND THERE'S A SPY TAG
AT EACH OF THOSE THREE SPY TAGS
PER TRIMER AND WE ALSO HAVE BP2
SPY TAG ON AAV AND IT ONLY
OCCURS AT A 1 IN EVERY 10
PROTEINS IN THE CAPSID AND END
UP WITH FIVE BP2 SPY TAGS.
THIS IS ESSENTIALLY HOW WE'RE
STARTING OFF AND WE NEED TO
COMBINE THEM.
SO I'M NOT GOING IN THE DETAILS
OF THIS FOR SAKE OF TIME BECAUSE
IT'S A LIGHTNING TALK BUT I
DEVISED AN ASSEMBLY AND FUR
FICTION TECHNIQUE WHICH YIELDS
THE AAVs.
I'LL SHOW YOU SOME OF THE
ASSEMBLY TESTS WITHOUT
PURIFICATION FIRST TO SHOW NICE
IMAGES OF AAVs AND THERE'S NO
CONTROL ON THE ADENOVIRUS AND
WHAT YOU CAN SEE IS THE ADD AAVs
ASSEMBLE NICELY IN MANY CASES.
I ESPECIALLY LIKE THIS ONE SO ON
AND SO FORTH AND YOU CAN GET A
NUMBER OF AAVs PER ADENOVIRUS
MAYBE AROUND 10 IF IT'S A GOOD
BATCH.
SO THEN THERE'S THE PURIFICATION
AND THESE ARE IMAGES AND YOU CAN
SEE BEFORE AND AFTER THE
PURIFICATION IT'S ABLE TO
ELIMINATE MOST THE FREE AAVs IN
THE AGGREGATES AND NOW I'M
DEVELOPING ASSAYS TO SHOW
MULTI-GENIC CO-DUCTION OF ADD
AAVs AND ALSO WORKING WITH OTHER
MEMBERS OF MY LAB TO DEVELOP A
MORE STREAMLINED ASSEMBLY
PROCESS THAT MAYBE WILL HAVE
HIGHER YIELDS AND ALSO ENFORCE
TO A DIFFERENT SET OF TYPES AND
ADENOVIRUS AND AAV TO BROADEN
THE OPTIONS FOR WHAT TYPES OF
CELLS ARE MOST SUFFICIENTLY
TRANSDUCED.
FINALLY I'M GOING TO TALK
BRIEFLY ABOUT ADD MS2 OR ADD
PHAGE THE FIRST AND PROBABLY THE
LEAST FULLY DEVELOPED TECHNOLOGY
BUT STILL VERY COOL.
SO WHAT AD MS2 IS A SMALL
BACTERIA PHAGE NOT THE TYPES
WHERE YOU SEE THE TAIL FIBERS
AND SPUTNIK LANDER LOOKING
THINGS BUT A BACTERIAL PHAGE
WHICH IS CARRIES RNA.
IT'S LIKE AN RNA VARIANT OF AD
AAV AND HAS APPLICATIONS.
ADENOVIRUS IS GREAT AS AN
INTRANASAL DELIVERY AND WE HAD A
VACCINE APPROVED BY THE HEALTH
OFFICIALS IN INDIA AND PASSED
PHASE III CLINICAL TRIALS AND
NOW ON THE MARKET IN INDIA AND
SO WHAT I'M DOING IS I AM TRYING
TO DEVELOP A WAY OF AVERAGE A
MORE EFFICACIOUS RNA ADENOVIRUS
VEHICLES WHERE THE ADENOVIRUS
SERVES AS A DELIVERY VEHICLE TO
TRANSDUCE THE MUCOSA ACTING AS
AN IMMUNITY BLOCK AT THE SITE OF
ENTRY AND AT THE SAME TIME
TRYING TO MAKE IT MORE EFFICIENT
THAN WHAT WE CURRENTLY HAVE
DEVELOPED IN THE LAB BY PROTECT
THE RNA MOLECULE WITH THIS
BACTERIAL PHAGE CELL.
I'M USING A SIMILAR SYSTEM OF
ASSEMBLY AND PURIFICATION.
YOU CAN SEE HERE WE HAVE THE
SAME PROCESS.
WE HAVE THE NICE AD MS2s IN THE
ROW OVER THERE AND THE CONTROL
AND THEN WE HAVE OUR
PURIFICATION PROCESS WHICH IS
VERY SIMILAR.
SO HOWEVER, THIS PURIFICATION
PROCESS HAS BEEN A LITTLE BIT
CUMBERSOME IN SOME CASES SO TO
STREAMLINE IT WE'RE ACTUALLY
WORKING WITH COLLABORATORS TO
ADD SPY TAG ON TO THE MATURATION
PROTEIN OF THE PHAGE WHICH IS A
SINGLE COPY PROTEIN IN THE
CAPSID.
THIS WILL ENABLE MUCH SIMPLER
ASSEMBLY PROCESS TO A CLICK AND
GO AND FOR PROOF OF PRINCIPLE
WE'RE WORK WITH 5CB5 TO BIND A
FLUOROPHOR AS PROOF OF CONCEPT
AND ACT AS AN ENHANCED VACCINE
RELEVANT TO WHAT OUR INTRANASAL
VACCINES ARE CAPABLE OF DOING
AND IT WILL BE YET ANOTHER
APPLICATION OF MOLECULAR GLUE
FOR THE PURPOSES OF GENE
DELIVERY.
WITH THAT I WILL CONCLUDE AND I
WILL TAKE QUESTIONS.
>> THANK YOU FOR THE TALK.
I'M INTERESTED IN THE DELIVERY
SYSTEM AND THE DES ASSEMBLY.
HOW DO YOU MAKE IT SO IT DOESN'T
DISASSEMBLE BEFORE IT GETS TO
ITS TARGET?
>> ESSENTIALLY THE VAULTS ARE
PRETTY STABLE UNDER
PHYSIOLOGICAL PH CONDITION BUT
THE DISASSEMBLY HAPPENS WHEN THE
PH GETS LOWER.
AROUND 5 OR 4 THE VAULTS START
TO COME APARD AND THIS IS
ACTUALLY SOMETHING THAT HAS BEEN
WELL DOCUMENTED IN THE
LITERATURE AND WHAT CAN HAPPEN
THEN IS YOU CAN IMAGINE ONCE THE
ENDOSOME BEGINS TO ACIDIFY WILL
RELEASE THE AAV THROUGH VAULT
DISASSEMBLY AND THE AAV WILL BE
ABLE TO EMPLOY IT'S OWN ACID
TRIGGERED PHOSPHOLIPASE TO GO
OUT TO THE NORMAL PATHWAY FOR
GENE TRANSDUCTION.
>> VERY COOL.
THANK YOU.
>> WELCOME.
ANY OTHER QUESTIONS?
ALL RIGHT.
THANK YOU VERY MUCH, EVERYONE.
>> WE'LL HAVE OUR SECOND
LIGHTNING TALK OF THE POSSESSION
BY PARISA YOUSEFPOUR TEMPORAL
CONTROLLED GENE EXPRESSION AND
SMALL MOLECULE SELF-REPLICATING
RNAs FOR CANCER IMMUNOTHERAPY.
>> HI.
THIS IS ACTUALLY MY FIRST IN
PERSON TALK TO A SYNTHETIC
BIOLOGY AUDIENCE AND THIS IS
LOOKING AT SELF-REPLICATING RNAs
FOR TEMPORAL CONTROL OF GENE
EXPRESSION.
SO CANCER IMMUNOTHERAPY HAS
REVOLUTIONIZED MANY FORMS OF
CANCERS AND A HALLMARK OF CANCER
IN IMMUNOTHERAPY IS THE
INDUCTION OF LONG LASTING
RESPONSES.
BUT THE LIMITATION IS THAT THESE
DURABLE RESPONSES ARE ONLY
OBSERVED IN A SMALL TRACTION OF
PATIENTS.
AND ALSO THESE IMMUNOTHERAPIES
CAN BE ASSOCIATED WITH ADVERSE
SIDE EFFECTS AND AUTO IMMUNE
REACTIONS.
SO THE GOAL OF OUR PROJECT IS TO
DEVELOP NEXT GENERATION RNA
THERAPEUTICS TO ENHANCE THE
EFFICACY AND SAFETY PROFILES OF
CANCER IMMUNOTHERAPIES.
AS I MENTIONED, THE RNA PLATFORM
WE WORK WITH IS SELF-REPLICATING
RNA AND WHAT OUR LAB USE DERIVED
FROM THE ALPHA VIRUS GENOME AND
BINDS STRUCTURAL AND
NON-STRUCTURAL PROTEINS AND
THESE INCLUDE PROTEINS LIKE THE
TRIMER AND CAPSID PROTEINS THAT
FORM THE VIRAL ENVELOPE.
IC MAKING THE REPLICONS AND THE
PROTEINS ARE TRANSLATED AN THIS
COPIES THE ORIGINAL STRAND OF
REPLICON AND GENOME AND THE SUB
GENOMIC TRANSCRIPT RESULTS IN
FOR EXAMPLE CYTOKINES FOR TRANS
IMMUNOTHERAPY.
BECAUSE OF THE SELF-AMPLIFYING
NATURE IT CAN TRANSFUSE IN THE
CELLS FOR A LONG TIME AND ALLOWS
FOR SUSTAINED GENE EXPRESSION
AND WHEN WE USE A REPORTED CARGO
WE WERE ABLE TO DETECT GENE
EXPRESSION AS INDICATED BY THE
SIGNAL FOR OVER MONTHS AND THIS
IS SIGNIFICANTLY LONGER THAN
WHAT CAN BE ACHIEVED WITH
CONVENTIONAL mRNA WHERE GENE
EXPRESSION ONLY LASTS A FEW
DAYS.
IN A PREVIOUS REPORT WE
CONSTRUCTED REPLICONS AND THESE
WERE ENCAPSULATED IN LIPID NANO
PARTICLES.
AND WE OBSERVED THIS REPLICON
FORMULATION WHEN THEY WERE
INJECTED INTO TUMORALLY AND
LOCALLY AND HAD SYSTEMIC
IMMUNOTHERAPY AND WERE ABLE TO
RESULT IN TUMOR REGRESSION IN
INJECTED AND UNINJECTED TUMORS.
THIS LED TO SURVIVAL 50% OF THE
ANIMALS.
IMPORTANTLY IN THIS WORK, WE
INTENTIONALLY USED THE CYTOTOXIC
LIPID NANO PARTICLE TO INDUCE
THE IMMUNOGENIC CELL DEATHS IN
THE INFECTED TUMOR CELLS AND
THESE CELL DEATHS OR ICD IS A
KEY CONTRIBUTOR TO THE STRATEGY
BECAUSE IT RELEASES THE TUMOR
ANTIGENS AND GENERATES AN IN
SITU VACCINATION EFFECT.
WE HYPOTHESIZED WE COULD ENHANCE
THE CURATIVE EFFICACY OF THIS
STRATEGY BY DELAYING THE
INDUCTION OF THE IMMUNOGENIC
CELL DEATHS TO KEEP THE INFECTED
CELLS AND IN FLAME THE TUMOR AND
RECRUIT THE IMMUNE CELLS AND
THEN TRIGGER THE CELL DEATHS TO
RELEASE THE TUMOR ANTIGENS.
SO, TO DO THIS INSTEAD OF USING
CYTOTOXIC LIPID PARTICLES WE
ENCODED FOR IL12 AND CYTOTOXIC
GASES AND TO DELAY THE
EXPRESSION OF THE GAS WE
INCORPORATED SYNTHETIC BIOLOGY
GENE CIRCUITS IN OUR REPLICATE
PLATFORM TO THE EXPRESSION CAN
BE TURNED ON AND OFF BUT ORAL
ADMINISTRATION OF THE SMALL
MOLECULE DRUG.
THE IDEA IS THEY INITIALLY KEEP
THE EXPRESSION OFF TO ALLOW FOR
IL12 EXPRESSION AND WE ADD THE
SMALL MOLECULE TO TURN IT ON AND
THEN KILL THE TUMOR AND RELEASE
THE TUMOR ANTIGENS.
THE REGULATED SIGNAL DEATH WE
USE IS AN ANTIBIOTIC.
IT'S BASED ON THIS D
DE-ESTABLISHED DOMAIN AND THIS
DD DOMAIN WHEN WE FUSE IT IT
FORMS DEGRADATION AND FOR
BINDING OF TMP STABILIZES THIS
FUSION AND RESULTS IN EXPRESSION
OF OUR GENE OF INTEREST.
SO TO INCORPORATE THIS TMP
RESPONSIVE GENE CIRCUIT IT TOOK
TWO APPROACHES.
IN THE DIRECT DD WE FUSED IT TO
THE GENE OF INTEREST AND WHEN
THERE'S NO TMP THE PROTEIN IS
TODAY GRADED AFTER TRANSLATION
AND GENE EXPRESSION IS TURNED
OFF WHEN WE ADD THE TMP THE
FUSION BECOMES STABLE AND GENE
EXPRESSION IS TURNED ON.
IN OUR SECOND APPROACH THE DD
CIRCUIT APPROACH WE TARGET THE
AMPLIFICATION MECHANISMS OF THE
REPLICON.
WE FUSE THE DD TO THE
NON-STRUCTURAL PROTEINS OF THE
REPLICON BACKBONE.
WHEN THERE'S NO TMP THE COMPLEX
IS DEGRADED AND REPLICON IS NOT
ABLE TO REPLICATE AND WE LOSE IT
AND THE RESULTING EXPRESSION IS
OFF.
IN THE PRESENCE OF TMP THE
MACHINERY IS RESTORED AND THE
REPLICON IS AMPLIFIES AND GENE
EXPRESSION IS TURNED ON.
AND WE CAN COMBINE THE
APPROACHES AND CONNECT THEM TO
THE GENE OF INTEREST.
AND WE DESIGN DIFFERENT GENE
CIRCUITS WITH DD FUSED THE FOUR
NON-STRUCTURAL PROTEINS OF THE
REM CON BACKBONE WITH OR WITHOUT
AN ADDITIONAL DD FUSED GENE OF
INTEREST.
WE TESTED THE CIRCUIT IN VITRO
AND LONG CANCER CELLS AND WITH
THE EXCEPTION OF NSD4 WHERE THE
FUSION ABOLISHES THE GENE
EXPRESSION THE FUSION OF DD TO
OTHER NSPs SHOWED AN EFFECTIVE
STRATEGY FOR REGULATING THE GENE
EXPRESSION.
AND AMONG THE DIFFERENT GENE
CIRCUITS WE DESIGN THE CIRCUIT
TO BOAST NSP3 AND OUR GENE OF
INTEREST SHOWED PROVIDE THE
STRONGEST REGULATION WITH OVER
100 FOLD DIFFERENCE IN THE BIO
LUMINESCENCE SIGNAL BETWEEN ON
AND OFF TMP STATES AND
IMPORTANTLY THE OFF STATE THE
EXPRESSION LEVEL WAS CLOSE TO
THE BACKGROUND INDICATING NON
EXPRESSION.
WE ALSO DID TITRATION
EXPERIMENTS AND SHOWED THE
LEVELS OF THE GENE EXPRESSION
CAN BE SUCCESSFULLY MODULATED BY
VARYING THE OF IT TMP DOSE.
WE CONTINUED WITH THE IN VIVO S
AND HERE WE INJECTED REPLICONS
INTERTEMPORALLY AND THE GENE
EXPRESSION WAS MONITORED
LONGITUDINALLY BY BIO
LUMINESCENCE IMAGING.
IN CASE OF THE CONSTITUTED
REPLICON THE BIO LUMINESCENCE
SIGNAL WAS SIMILAR WITH OR
WITHOUT TMP AS EXPECTED BUT
WITHOUT REGULATED CIRCUIT IN THE
ABSENCE OF TMP THE SIGNAL WAS
MINIMAL AND CLOSE TO BACKGROUND
BUT WHEN WE ADD THE TMP IT
SIGNIFICANTLY ELEVATED AND
SHOWED LEVELS SIMILAR TO CLOSE
TO THAT OF CONSTITUTED REPLICON.
AND WE DESIGN GENE CIRCUITS AND
THE FIRST GENE CIRCUIT WE DESIGN
ACTUALLY FAILED AND WHEN WE LOOK
AT THE CELL VIABILITY WE
ACTUALLY SAW NO CYTOTOXICITY AND
NO REGULATION.
WE HYPOTHESIZED THIS MIGHT HAVE
TO DO WITH THE DIFFERENCE
BETWEEN DD AND GAS THERAPY.
THE FIRST DESIGN WE HAD, WE HAD
THE DD AT THE END TERMINIS AND
USED THE LINK BETWEEN THE TWO.
WE DESIGN DIFFERENT FUSIONS WITH
DIFFERENT LINK SEQUENCES AND
EXPERIMENTED WITH THE FUSION
SITE OF DD.
IN TERMS OF LINKER WE HAD THREE
DIFFERENT LINKERS A LONG
FLEXIBLE AND SHORT FLEXIBLE
LINKER AND RIGID LINKER.
AGAIN THE CIRCUITS WERE TESTED
IN KP LONG CANCER CELLS AND
FOUND IT WAS CRITICAL TO HAVE DD
FUSED AT THE C TERMINIS AND
AMONG THE LINKERS WE TEST THE
SHORT FLEXIBLE LINKER AND THE
RIGID LINKER PROVIDE GOOD
REGULATION IN TERMS OF VIABILITY
AND IL12 EXPRESSION.
SO, FOR OUR THERAPEUTIC STUDY WE
USED FUSION WITH A SHORT LINKER
AND THE CIRCUIT WAS INJECTED
INTERTUMORALLY AND TESTED THREE
EXPRESSION PATTERNS HAVING THE
EXPRESSION CONSTANTLY ON BY
MAINTAINING TMP THROUGHOUT THE
STUDY AND CONSTANTLY OFF BY
REMOVING TMP THROUGHOUT OR
KEEPING THE EXPRESSION OFF FOR
TWO DAYS AND TURNING IT ON BY
ADDING TMP.
WE WERE HAPPY TO SEE THIS OFF/ON
REGIMENT WAS ABLE TO ENHANCE THE
THERAPEUTIC EFFICACY OF THIS TO
THE IL GAS FORMULATION.
TO SUMMARIZE WE HAVE ENGINEERED
GENE CIRCUITS TO SMALL MOLECULE
DRUG TRIMETHOPRENE AND HAVE
INDUCTION OFFO GENIC --
IMMUNOGENIC CELL DEATHS AND BY
DELAYING THIS WE CAN ENHANCE THE
IL12 REPLICON.
AND WITH THAT I WOULD LIKE TO
THANK MY POSTDOC ADVISER AND ALL
OTHER MEMBERS OF THE FLAG WHO
CONTRIBUTED TO THE PROJECT AND
AND FUNDING AGENCIES AND OF
COURSE NIH.
THANK YOU, GUYS.
>> VERY NICE DATA.
I'M CURIOUS ABOUT THE LENGTH OF
THE REPLICON VERSUS THE DELIVERY
EFFICIENCY.
THE PIECE OF mRNA IS PRESUMABLY
THE LESS COPIES YOU WOULD
DELIVER INTO THE CELL AND
CERTAINLY YOU WOULD GET THE
AMPLIFICATION OVER TIME.
AS I'M CURIOUS, YOU MUST HAVE
SEEN SOME OF THOSE CHALLENGES
AND CAN YOU COMMENT ON THE
PLUSES AND MINUSES OF A LONGER
REPLICON VERSUS A SHORTER PIECE
OF mRNA THAT CANNOT REPLICATE
BUT CAN DELIVER HIGHER DOSES AT
THE ONSET.
>> SO, THAT'S A GOOD POINT BUT
FOR OUR BIO ILLUILLUMOESSENCE A
REPLICONS ALLOW FOR LONG-LASTING
GENE EXPRESSION AS WITH mRNA
EXPRESSION ONLY LASTS A FEW
DAYS.
EVEN WITH A HIGHER DOSE USING
mRNA REPLICON STILL PROVIDES
THE, I GUESS, WINS.
>> GOOD MORNING.
THANK YOU VERY MUCH FOR THE
PRESENTATION.
IT'S A WONDERFUL SYSTEM.
IN THE LUCIFERASE EXPRESSION AND
OF THE SIGNAL THAT'S WITH THE
SYSTEM WITH THE TWO DD SYSTEMS
IN IT.
THE PROFILE THE EXPRESSION
DIFFERENT IF YOU JUST USE ONE OR
THE OTHER?
IT'S INTERESTING HOW IT GOES UP
A LITTLE BIT AND A LITTLE BIT
MORE AND THEN BACK DOWN.
DO YOU HAVE ENOUGH DATA TO SEE
HOW THE DIFFERENT ANALOGS MIGHT
GIVE DIFFERENT EXPRESSION
PATTERNS?
>> YEAH, THANK YOU FOR THE
QUESTION.
SO WE ACTUALLY INITIALLY STARTED
WITH THE DIRECT DD CIRCUIT AND
HAD IT FUSE TO OUR GENE OF
INTEREST AND THEN THAT ONE WAS
SUPER IN VIVO.
THAT'S WHY WE WENT BACK TO LIKE
DESIGN BOARD AND THEN WE CAME UP
WITH THE STRATEGY OF HAVING THE
DD ALSO FUSE TO NSBs.
>> ANY OTHER QUESTION?
THANK YOU.
>> THANK YOU FOR THIS MORNING'S
SPEAKERS.
WE'RE GOING TO BREAK FOR 30
MINUTES SO COFFEE AND SOME
PASTRIES ARE IN THE ROOM ACROSS
FROM US.
THANK YOU.
LIKE TO INTRODUCE OUR NEXT
SPEAKER, DR. BORHANI AND GROWS
GINKO OPPORTUNITIES IN THE
GOVERNMENT AND LED TEAMS TO WIN
THE LARGEST GOVERNMENT AWARDS
INCLUDING PRE-CELL THERAPEUTIC
SYNTHESIS FROM DARPAR AND
SECURED AN NIH RADX AWARD FOR A
TESTING PROGRAM AND HELPED GINKO
EXPAND INTO BIO SECURITY.
HE WON GINKO'S FIRST PHARMA
CONTRACT WITH LILY AND INITIATED
AND CO-LED THE ONE WITH
NOVONORDIS AND GOT HIS Ph.D.
FROM M.I.T.
WELCOME TO THE STAGE, DAVID.
>> THANK YOU FOR THE INVITATION
TO SPEAK HERE TODAY.
WHAT A WANTED TO TELL YOU ABOUT
TODAY IS GINKO'S CELL
PROGRAMMING PLATFORM.
WHERE WE STARTED AND WHAT IT
LOOKS LIKE AND WHAT IT'S LIKE TO
RUN ON THE PLATFORM AND WHERE WE
THINK WE'RE GOING.
AND GIVE YOU SOME EXAMPLES
MOSTLY FROM THE PHARMA SPACE.
THERE'S ONE I HOPE TO GET TO AT
THE END THAT WILL PREP US FOR
LUNCH.
OKAY.
SO, GINKO STARTED 15 YEARS AGO
AND ON THE LEFT SIDE YOU SEE ONE
OF OUR FIVE FOUNDERS, TOM
KNIGHT.
TOM WAS A PROFESSOR IN THE
ELECTRICAL ENGINEERING
DEPARTMENT AT M.I.T.
HAD, HAD AT THAT POINT A LONG
CAREER PROGRAMMING COMPUTERS AND
I'M BLANKING ON THE NAME OF THE
PERSON WITH HIM THERE.
THEY'RE PROGRAMMING A MINI
COMPUTER.
HOW TIMES HAVE CHANGE.
AND TOM WANTED TO DO EXPECT
DIFFERENT THAN PROGRAMMING
SILICON AS TIME WENT ON AND THE
CELLS BIOLOGY WAS NOTHING BUT A
COMPUTER RUNNING ON CODE LIKE
THE SILICON COMPUTER AND NOT
RUNNING ON 1s AND 0s BUT As, Gs
AND Ts AND WENT BACK TO GRADUATE
SCHOOL AND STARTED UP A LAB
DOING BIOLOGY AND THE REST IS
HISTORY.
AND ALSO SHOWN ON THE RIGHT SIDE
THEN ARE OTHER FOUR CO-FOUNDERS,
ARI, JASON, RUSHMA AND OSMAN ALL
STILL WITH GINKO, CEO, COO,
CHIEF TECHNOLOGY OFFICER, I
GUESS IS HIS TITLE AND STRATEGY
IS WHAT AUSTIN DOES.
AND A RECENT PICTURE FROM JUST A
COUPLE YEARS AGO.
AND YOU CAN GET A GLIMPSE OF
WHAT OUR BUILDING LOOKS LIKE ON
THE INSIGHT.
-- INSIDE.
SO JUST A LITTLE BIT MORE DETAIL
ABOUT GINKO.
WE'RE A PUBLIC COMPANY.
WE WENT PUBLIC IN 2021.
TIME FLIES, COVID AND ALL.
AND HOW WE'VE POSITIONED
OURSELVES IS AS AN INNOVATION
PARTNER FOR BOTH THE COMMERCIAL
SPACE AND GOVERNMENT SPACE.
AND WE'RE WORKING ACROSS
INDUSTRIES AND IN PHARMA IN
PARTICULAR WE'RE WORKING ACROSS
THERAPEUTIC MODALITIES.
I'LL TELL YOU MORE ABOUT THAT.
SO OVER THE LAST 15 YEARS WE'VE
JUST BEEN BUILDING A LARGE OUT
MATED PLATFORM AND THE SOFTWARE
NEEDED TO RUN IT AND THE
CODE-BASE ON WHICH IT RUNS IN
ORDER TO ENABLE JUST EVER MORE
APPLICATIONS IN SYNTHETIC
BIOLOGY.
AND A BIG PUSH IN THE PHARMA
AREA AND WE BROUGHT ON TO OUR
BOARD A COUPLE YEAR AGO, BARE
REGELDMAN FROM KITE AND RUSHMAN
ROMANI FROM VERTEX.
SO PHARMA APPLICATIONS ACTUALLY
REPRESENT A BIT OVER 50% OF WHAT
GINKO DOES AND YOU'LL SEE ON THE
NEXT SLIDE EVERYTHING ELSE WE'RE
IN.
AND DURING COVID WE STOOD UP A
WHOLE BIO SECURITY UNIT CALLED
CO-CENTRIC.
HALF IS PHARMA AND HALF IN BIO
AND THE OTHER HALF AND THAT'S
CONCENTRIC.
AND WE HAD STOOD UP AN ENTIRE
TESTING NETWORK AND NOW
EXPANDING INTERNATIONALLY.
SO THIS IS MY FAVORITE SLIDE I
EVER SHOW BECAUSE IT KIND OF
ENCAPSULATES IN A COMPLETE
NUTSHELL.
WE ARE WORKING WITH LARGE
COMPANIES UP AT THE TOP.
START UPS AT THE BOTTOM PHARMA
AND WELLNESS IN FOOD AND
AGRICULTURE AND THERE'S A
TRANSITION FROM PHARMA AND
ENDING UP AT INDUSTRIAL BIO TECH
AT THE RIGHT SIDE.
IT'S JUST I COULD SPEND AN HOUR
TALKING ABOUT EACH ONE OF THESE
COMPANIES AND WHAT WE'RE DOING
BUT IF I WERE TO JUST HIGHLIGHT
A COUPLE OF THEM, RECENT
ANNOUNCEMENT OF A VERY LARGE
DEAL WITH PFIZER TO DEVELOP
RNA-BASED THERAPEUTICS.
WE MENTIONED LILLY AS AN ENZYME
DEALER AND BIO GEN WE'VE BEEN
WORKING ON AAV MANUFACTURING
WITH THEM AND ANTHEIA AND IT'S A
COMPANY SPUN OUT AND FORMED FROM
THE PLATFORM AND BRING IN
VENTURE INVESTORS THAT CAN
PROVIDE SOME OF THE CAPITAL.
GINKO PROVIDES THE PLATFORM ON
WHICH THESE COMPANIES' PROGRAMS
RUN AND ANTHIA MAKE DRUGS THAT
TYPICALLY COME FROM PLANT BUT
INSTEAD USING SYNTHETIC BIOLOGY
AND THE POWER OF THE PLATFORM TO
MAKE THAT HAPPEN.
OKAY.
AND WE HAVE A FAIR AMOUNT OF
GOVERNMENT FUNDING.
WHAT WE USE GOVERNMENT FUNDING
FOR IS TO PUSH THE BOUNDARIES OF
WHAT'S POSSIBLE AND YOU SEE THE
DARPA LABEL AND WOULD LOVE TO
EXPAND TO OTHER AGENCIES.
AND I FORGOT TO PUT IT ON THERE
BUT RECENTLY ANNOUNCED AWARD
THAT GINKO'S PART OF WITH THE
USDA WHICH IS OUR FIRST WITH
THEM.
WHY ARE PEOPLE WORKING WITH
GINKO?
WE HAVE THE INNOVATION AND BRING
THE CAPABILITIES THEY WOULD LIKE
TO HAVE IN HOUSE BUT DON'T WANT
TO TAKE THE TIME AND EXPENSE TO
DO IT.
SO IF YOU THINK ABOUT LIKE WHAT
IT TAKES TO MOVE INTO A NEW AREA
IT'S A BIG DEAL.
YOU HAVE TO ALLOCATE THE
LABORATORY RESOURCES AND WHO
WILL LEAD IT AND HIRE.
SO IT'S A LONG START-UP TIME AND
WHAT DO YOU DO THREE YEARS LATER
IF YOU THINK IT'S NOT A GREAT
IDEA AND NEED TO DO SOMETHING
ELSE INSTEAD?
WHERE A COMPANY LIKE GINKO COMES
IN AND THIS APPLIES TO
COMMERCIAL COMPANIES AND THE
GOVERNMENT AS WELL IS WE HAVE
THE INFRASTRUCTURE BUILT.
IT'S ABLE TO RUN MANY PROGRAMS
SIMULTANEOUSLY.
I THINK WE HAVE 100 CURRENT
PROJECTS RUNNING AT THE SAME
TIME AND STOP AND START AND
BRING IN SOMETHING NEW THAT
REALLY CAN GET YOU GOING
QUICKLY.
I HAVE A SLIDE I DIDN'T PUT ON
HERE THAT SORT OF SHOWS THAT
GRAPHICALLY BUT YOU'D LIKE TO BE
ABLE TO TURN ON AND TURN OFF AND
THIS IS ESPECIALLY TRUE FOR
SMALLER COMPANIES SAY SMALL
START-UP COMPANIES AND WANT TO
PUSH AS HARD AS YOU CAN INTO A
PLATFORM LIKE GINKO.
I WANT TO TEST TENS OF THOUSANDS
OF MY DESIGN AAV OR BIOLOGIC OR
WHATEVER IT IS AND YOU'RE
SUCCESSFUL AND YOU GO TO THE
CLINIC AND ALL YOUR TIME AND
MONEY AND EFFORT IS FOCUSSED ON
THE CLINICAL TRIALS AND YOU'VE
GOT TO GET TO THAT FIRST WIN
BEFORE THEN YOU CAN START YOUR
BACK UP PROGRAMS.
IT'S LIKE THIS BOOM AND THEN
BUST IN TERMS OF THE R&D
LABORATORIES.
SO GINKO CAN HELP SMOOTH THAT
OUT.
OKAY.
SOME VERY NICE WORDS FROM FOLKS
AT NOVO NORDISK.
IF YOU LOOK AT THE PRESS
RELEASES AND I HAVE TO BE
CAREFUL WHAT I SAY HERE.
IT'S ABOUT MANUFACTURING IN
MICROORGANISMS AND EXPANDING THE
CHEMICAL UNIVERSE AND YOU ALL
CAN READ BETWEEN THE LINES.
WE HAD A BIG WILL PROGRAM AND
BAYER SAID YOU GUYS ARE DOING
GREAT AND LET'S MOVE THAT TO
GINKO AND LET'S CONTINUE THE
COLLABORATION AND AS A RESULT OF
THAT GINKO ACQUIRED GREENHOUSE
FACILITIES IN CALIFORNIA AND A
PROJECT THAT GOES UP TO 3,000
LITER.
I'LL FINISH WITH THIS NOTE FROM
BRYAN VANDAL ABOUT THE FUTURE OF
A.I. IN BIOLOGY AND MIKE TOUCHED
ON THIS AT THEN OF HIS TALK AND
INDEED THIS IS WHERE WE'RE
GOING.
WE ANNOUNCED JUST AT THE END OF
AUGUST A RELATIONSHIP WITH
GOOGLE CLOUD WHERE WE HAVE
PREFERENTIAL ACCESS TO THEIR
PROCESSING UNITS PRECISELY TO DO
THIS TO LEVERAGE THE AMAZING
AMOUNT OF DATA GINKO HAS
GATHERED OVER THE YEARS AND
ABILITY TO GATHER MORE DATA IN
THE BIOLOGICAL REALM AND REALLY
TRANSFORM HOW IT IS WE'RE DOING
THESE KINDS OF DESIGNS IN THE
PROTEIN SPACE, IN THE DNA, RNA
SPACE IN THE BIO SECURITY SPACE
AS WELL.
I REALIZE I HAVE NO PICTURES OF
OUR LABORATORY.
THIS IS AN OLD PICTURE BUT GIVES
A SENSE OF HOW MANY ROBOTS AND I
DON'T KNOW HOW MANY AT THIS
POINT AND THE WHOLE POINT IS TO
AUTOMATE THE UNIT OPERATIONS
THAT TAKE PLACE AS YOU'RE
ENGINEERING AN ORGANISM.
BOTH AT THE DESIGN STAGE AND
HAVE SET PROGRAM PACKAGES THAT
IF YOU NEED TO GO DESIGN
AAV 9 IN BLUE AND ON THE LEFT
SIDE WE HAVE CAPSIDS THAT HAVE
BEEN VALIDATED IN NON-HUMAN
PRIMATES.
ON THE RIGHT ARE THE EARLIER
ONES IN MICE OR PERHAPS STILL IN
VITRO CAPSID AND THIS THE
PASSAGING PROCESS.
MAKE THE LIBRARIES SO 47 STARTED
WITH AAV 9.
ALL KINDS OF VARIANTS WENT INTO
PIGS AND THE WINNERS ARE AT THE
TOP OF THAT PANEL AND IT'S HOW
PREVALENT ARE THE READS IN A
GIVEN TISSUE AND THE SIZE OF THE
BUBBLES ARE HOW MUCH OF AN
INCREASE WAS THAT OVER WHERE
THAT PARTICULAR CAPSID STARTED.
AND THEN THE WINNERS IN THE PIG
WENT INTO THE MOUSE AND THE
WINNERS IN THE MOUSE WENT INTO
THE MONKEYS AND THAT BIG ONE AT
THE TOP IS NUMBER 47.
WE CAN THINK OF IT AS AN AAV9
WITH INTERESTING MUTATIONS AND
WHAT THEY DO IS THEY LET IT GO
TO MANY OF THE SAME TISSUES THAT
AAV 9 DOES GIVES HIGHER
EXPRESSION.
THAT'S SHOWN IN THESE DATA
GRAPHS ACROSS DIFFERENT TISSUES
AND IN THE IMAGES IN THE
IMMUNOHISTO CHEMISTRY.
AND THAT ONE WAS IN MICE AND
THIS IS IN MONKEYS INJECTED INTO
THE BRAIN OF THE MONKEYS AND YOU
CAN SEE 47 IS LIGHTING UP ON THE
RIGHT SIDE.
INTERESTINGLY IT SHOWS MUCH
HIGHER EXPRESSION IN THE KIDNEY.
AND THAT'S SHOWN ON THE RIGHT
PANEL AND QUANTITATIVELY THEN
OVER HERE THE WIDER SPREADING OF
THE GENE DELIVERY IN THE KIDNEY.
SO WHAT DO YOU DO WITH A CAPSID
LIKE 47 WORKING BETTER BUT GOING
TO DIFFERENT TISSUES?
HOW DO YOU GET SPECIFIC THERAPY?
THIS IS ANOTHER PLACE WHERE THE
GINKO PLATFORM CAN COME IN.
WE HAVE A DIFFERENT TECHNOLOGY
WHICH IS HOW DO I FIND A
SPECIFIC PROMOTER?
IT'S BASED ON SELF-CLEAVING
RNAs.
IF WE USE THAT CHEMISTRY TO FIND
THE RIGHT PROMOTERS WE MARRY
THEM AND ARE FURTHER LONG IN
ADVANCING THE THERAPY.
WHAT THAT IS AND WITH A COMPANY
IN CALIFORNIA CALLED
CIRCULARARIS, PROMOTERS GET
INCORPORATED INTO THE CIRCULAR
RNAs AND YOU CAN ANALYZE THEM IN
THE CELL TYPE OF CHOICE AND DO A
BAR-CODED READ OUT TO SEE WHICH
ONES ARE THE WINNERS.
AND ONE SUCH EXPERIMENT IS
SUMMARIZED HERE.
WE WERE LOOKING FOR PROMOTER AND
ENHANCER ELEMENTS THAT WOULD
GIVE US PREFERENTIAL EXPRESSION
EITHER IN THE LIVER OR IN THE
LUNG AND THE GRAPH SHOWS LI
EXPRESSION IN BOTH TISSUES IN
GREEN GOING UP TO THE TOP IN
PURPLE, HIGH IN THE LUNG, LOW IN
THE LIVER OR INDEED REPRESSED IN
THE LIVER GOING FURTHER TO THE
LEFT IN THE BLUE AND THEN SOME
LIVER SPECIFIC REPRESSORS THAT
HAVE NO THE LUNG ON IN THE FAR
LEFT AND THE DIFFERENT COLORS
REPRESENT ACTUAL GENETIC
SEQUENCES.
SO THIS WAS A SCREEN OF 800,000
REGULATORY ELEMENTS THAT WERE
COBBLED TOGETHER BY A VARIETY OF
TECHNIQUES.
SO IT'S REALLY FINDING NEEDLES
IN A HAYSTACK AND THAT'S REALLY
ONE OF THE POWERS OF OUR
PLATFORM.
OKAY.
SO, THAT'S WHAT THE INTRO SLIDE
WAS FOR AND WANTED TO SAY ASOME
WORDS ABOUT LPMs AND DOING
CELL-FREE PHOTO SYNTHESIS AND
THE IDEA IS TO DO THINGS LIKE
DISTRIBUTED MANUFACTURING A
COUPLE PICTURES I DREW FROM PAST
DARPA PROGRAMS FROM THE FIELD OR
DISTRIBUTED MANUFACTURING OF
THERAPEUTICS.
WE HAVE THE BIO MOD AND PHARMACY
ON DEMAND IN THE MIDDLE AND AT
THE RIGHT FROM UMBC AND TIM
JAMISON AT M.I.T.
SO, GINKO'S TRYING TO, IF YOU
WILL, BRING THE NEXT GENERATION
HERE AND THE IDEA WITH THE RPM
PROGRAM I'M SURE YOU'LL HEAR
MORE FROM MIKE AND I DON'T WANT
TO STEAL HIS THUNDER BUT
BASICALLY MAKE THERAPEUTIC
PROGRAMS USING CELL-FREE AND
ENSURE YOU MAKE A VERY PURE AND
CORRECTLY HUMANLY GLYCOSYLATED
PROTEINS WHICH IS ACTUALLY QUITE
DIFFICULT.
SO GINKO'S LEADING THE EFFORT.
WE HAVE A WONDERFUL TEAM AND THE
KEY PLAYERS ARE PICTURED HERE
BUT I WANTED TO HIGHLIGHT OUR
COLLABORATORS AT IMPERIAL
COLLEGE LONDON AND THEN AT
NATURE'S TOOLBOX WHICH IS A
SMALL START OFF FROM LOS ALAMOS
LAB IN NEW MEXICO.
AND A SCHEMATIC ABOUT WHAT WE'RE
DOING WHICH INVOLVES AS YOU
MIGHT EXPECT, DISCOVERY,
OPTIMIZATION AND THEN
DEPLOYMENT.
IT'S DESIGN, BUILT TEST JUST
TAKEN TO THE NEXT STEP.
OKAY.
AN ACTUAL CASE STUDY.
SO WE'VE BEEN WORKING WITH A
COMPANY CALLED SYN LOGIC
BRINGING LIVING THERAPEUTICS TO
THE CLINIC AND HOPEFULLY SOON
BEYOND.
SO OUR COLLABORATION WITH THEM
DATES BACK NOW I THINK ABOUT SIX
YEARS.
IT COVERS SOMETHING LIKE 10
PROGRAMS AND THIS IS ONE OF
THOSE.
THEY WANTED TO COME UP WITH A
LIVING ORGANISM, AN E. COLI YOU
EAT TREATING THIS RARE DISEASE
CALLED HOMOCYSTINURIA AND CAN WE
MAKE WHAT IS FURTHER ENGINEERED
BY PUTTING THE RIGHT METABOLISM
IN IT SO WHEN YOU EAT THIS IT
WILL CHEW UP THE METHIONINE AND
THE DATA GRAPHS SHOW THE
OPTIMIZATION ATOP OF ONE OF THE
ENZYMES IN THE DESIGN PATHWAY.
OTHERS HAT HIGHER ACTIVITY BUT
WHEN PUT IT IN THE CONTEXT OF
THE FULL ORGANISM AND MAYBE IT'S
NOT THE BEST CLINICAL CANDIDATE
AND LOTS OF VARIANTS AND COPY
NUMBER TO OPTIMIZE THE OVER ALL
METABOLISM AND IT'S SHOWN AT THE
BOTTOM GRAPH.
THIS IS THE DEPLETION OF
METHIONINE AND CYSTINE AND THE
GRAPH AT THE BOTTOM KIND OF RED
IS THE DRUG COMPARED TO THE
CONTROLS OR THE EMPTY E. COLI
VECTOR.
THE EMPTY E. COLI.
THIS DID THE JOB SO IT
PROGRESSED.
AND THIS IS NOW CALLED SYNB1353
AND FINISHED PHASE I AND GOING
TO PHASE II.
THIS IS MY WRAP-UP, PRODUCTION
AND SCALE.
I MENTIONED OUR ABILITY TO
SCREEN THINGS LIKE PROMOTERS AND
FIND ONES THAT WORK WELL AND WE
PRODUCED A WORKFORCE FOR
INDUSTRIAL BIO TECHNOLOGY.
IT IS A SHETLAND PONY IN THE
PHARMA SPACE BUT IT'S GROWING OR
MAYBE WILL GROW ESPECIALLY IF WE
CAN ENGINEER IT TO MAKE HUMAN
GLYCANS EFFECTIVELY.
WE HAVE A PICIHA PRODUCING
WITHOUT METHANOL PRODUCING WHICH
IS STANDARD IN THE ACADEMIC
SPACE.
A LITTLE BIT IN THE INDUSTRIAL
SPACE BUT PEOPLE HATE IT BECAUSE
YOU DON'T WANT TO WORK WITH 50
LITER FERMENTERS YOU HAVE TO
PUMP METHANOL INTO.
WE HAVE A METHANOL-FREE SYSTEM
THAT WORKS WAY BETTER THAN THE
METHANOL INDUCED SYSTEM WHICH
HAS BEEN AMAZING.
THE EXAMPLE AT THE BOTTOM IS A
FLUORESCENT PROTEIN AND WE HAVE
AN ENTIRE FERMENTATION GROUP AND
THE AMBER 250s OVER 300 UNITS.
WE'RE USING THESE THINGS IN ALL
KINDS OF PROGRAMS TO OPTIMIZE
THE STRANDZ --
THE STRAINS THAT COME IN AND THE
PREDICTION ON THE LEFT WHICH IS
HOW DO I NEED TO RUN THE
FERMENTER AS DETERMINED IN THESE
LITTLE THINGS ONLY THIS BIG.
THE AMBER PREDICTION WAS IN THE
LITTLE BOX AT THE FAR RIGHT, THE
UPPER BOX.
THE CUSTOMER WANTED TO DO A
PILOT SCALE BECAUSE NATURALLY
THEY DIDN'T BELIEVE US.
THEY RAN THE PILOT EXPERIMENT.
THAT'S THE BLUE LINE THEN RAN
THE COMMERCIAL SCALE AND TRACKED
TO PILOT AND GOT TO WHERE WE
SAID IT WOULD GET TO AND CAME
BACK AND SAID THIS IS TOO HARD
TO RUN IN A PLANT.
WE CAN'T TURN THE VALVES THAT
FAST, IF YOU WILL.
SO CAN YOU COME UP WITH A
SIMPLER PROCESS.
WE RE-ENGINEERED THE PROCESS AND
THAT'S THE LOWER PURPLE BOX AT
THE TOP RIGHT.
SIMPLER PROCESS NOW UP AND
RUNNING.
WE HAVE A PARTNER FACILITY
COMPANY CALLS FERMIC BASED IN
MEXICO CITY AND MANY PARTNERS
HAVE PRODUCING WITH FERMIC AND
THESE THE TANKS THAT HOLD THE
CASTOR OIL THAT GOES IN THE
FERMENTATION AND THEY'RE 50,000
LITERS.
IT GIVES A SENSE OF HOW BIG IT
IS.
IT'S PRETTY BIG.
WE USED THIS SYSTEM WITH OUR
SPIN-OFF COMPANY MOTIF IN THE
ENGINEERED PROTEINS FOR FOOD
SPACE.
AND THEY WANTED A PROTEIN THEY
COULD PUT INTO BURGERS.
THEY WANTED SOMETHING TO MAKE
THE BURGERS RED AND TASTE GOOD.
WE STARTED AT THE BOTTOM LEFT
AND DID A HUGE SCREEN, THOUSANDS
AND THOUSANDS OF GLOBIN
CONTAINING MOLECULES, MYOGLOBIN
AND OTHERS AND WE SCREENED AND
OPTIMIZED AND YADDA, YADDA, IN
THE END WE DELIVERED THE WINNER.
THE IRONIC THING IS THE WINNER
IS MYOGLOBIN AND CHEETAH WAS THE
RUNNER UP SO MAYBE SOME DAY
THEY'LL DO CHEETAH BURGERS.
THEY BROUGHT THIS TO MARK AND
THIS IS GOING TO BE COMING UP
SOON AND HAPPY TO TAKE ANY
QUESTIONS YOU HAVE.
THANK YOU.
>> I'M CURIOUS IF YOUR SERVICES
CAN EXTEND TO SMALL-SCALE
SPINOFFS TO ACADEMIC LABS JUST
GETTING STARTED IF THERE'S A
PILOT PROCESS THAT CAN BE RUN
FOR THAT TYPE OF LEVEL OR IF
GINKO'S JUST TOO BIG ESSENTIALLY
TO THAT LEVEL OF LABORATORY OR
ORGANIZATION CAN AFFORD?
>> GOOD QUESTION.
THANK YOU.
SO IF YOU CAST YOUR MIND BACK TO
THE PICTURE WITH ALL THE LOGOS,
I WOULD SAY ABOUT HALF THE
COMPANIES MAYBE TWO-THIRDS THAT
WE'RE WORKING WITH ARE VERY
SMALL.
SO THEY'RE START UPS.
WE'RE HAPPY TO ENTERTAIN
POSSIBILITIES AND TALK ABOUT IT.
BOTH FROM THE POINT OF VIEW OF
CAN WE WORK TOGETHER IN SOME
SORT OF COMMERCIAL SENSE TO
BRING THE SMALL COMPANY TO ITS
INFLECTION POINT, WHATEVER THE
NEXT VALUE INFLECTION POINT IS
BUT ALSO TO PARTNER ON
CUTTING-EDGE RESEARCH.
SO GO AFTER GOVERNMENT FUNDING
THAT WILL LED US TOGETHER
SOMETHING BIGGER THAN WE CAN DO
ALONE.
ABSOLUTELY.
>> THAT'S VERY GOOD NEWS.
THANK YOU.
>> I WONDERED ABOUT THE SCALE OF
AUTOMATION YOU GUYS ARE WORKING
WITH.
SCREENING FOR THE DIFFERENT
ITERATIONS BUT HOW MUCH BENCH
WORK IS ACTUALLY GOING ON
BYPRODUCT THE SCENES, IS IT PLUG
AND PLAY.
>> IDEALLY THE ROBOTS WOULD BE
DOING ALL THE WORK BUT AS YOU
WALK THROUGH AND TOUR GINKO LABS
YOU'LL SEE WE HAVE ABOUT 1200
PEOPLE IN THE LAB.
SCIENTISTS.
IT'S ABOUT 600, I GUESS.
THERE'S AN ENTIRE SOFTWARE STACK
THAT RUNS THE WHOLE THING FROM
DESIGN OF EXPERIMENT TO
SCHEDULING ON THE ROBOTS TO
RUNNING OF EXPERIMENT, BANKING
AND ANALYZING AND LEARNING FROM
THE DATA.
THAT'S WHY WE HAVE 120 PEOPLE
DOING THAT BUT AS YOU WALK
AROUND YOU'LL SEE PEOPLE AND IT
DEPENDS ON THE PROJECT.
SOMETHING LIKE THE DARPA RPM IS
A GOOD EXAMPLE.
IT'S CUTTING-EDGE
EXPERIMENTATION AND FOOLING
AROUND AND YOU'LL SEE STUFF IN
THE LABORATORY WITH PEOPLE AND
IT'S LIKE OKAY, NOW I HAVE A
LIBRARY OF 3,000 GLYCOTRANSFER
A
GLYCOTRANSFERASS AND HAVE TO GET
PUSH BUTTON AND SOMETIMES YOU'LL
SEE PEOPLE LOADING PLATES BUT I
DON'T KNOW HOW MANY ROBOTS TOTAL
NOW.
THE NUMBER 300 PLUS WAS BOUNCING
AROUND AND WE BROUGHT IN NEW
AUTO MATION THE RECONFIGUREABLE
AUTOMATED CARTS WHERE EACH
MACHINE THAT DOES A UNIT
OPERATION LIKE A PLATE SEALING,
CENTRIFUGATION ARE INSIDE OF BOX
ON WHEELS AND YOU CAN LITERALLY
DRIVE THEM AROUND AND PLUG THEM
INTO A RAILROAD TRACK THAT
DRIVES THE PLATES AROUND.
IF YOU WANT A NEW WORK FLOW YOU
LINE UP THE PARTS IN ORDER AND
YOU'RE UP AND RUNNING.
WE ARE DEPLOYING MORE AND MORE
OF THOSE.
>> VERY COOL.
THANK YOU.
>> THANK YOU.
ONE QUESTION I HAVE STRUCK BY
THE NUMBER OF PROJECTS, ENZYMES
EXPRESSED, EASIES AS YOU FLASH
UP BILLIONS OF MOLECULES AND
WONDERING HOW THAT CONTRIBUTE TO
A.I., CURIOUS, ARE THERE IS
THERE A FRACTION OF MAKING THAT
OPEN SOURCE AND RECOGNIZING SOME
IS INTERNAL AND MUCH FUNDED BY
GOVERNMENT GRANTS AND TRYING TO
MOVE IN A NEW WORLD OF A.I.
WHERE WE CAN LEVERAGE THE
INFORMATION AND WONDERING WHAT
THE DISCUSSIONS ARE LIKE INSIDE
GINKO.
>> GREAT QUESTION.
THE WORK WE'RE DOING LEVERAGING
THE GOOGLE RESOURCES IS BRAND
NEW.
WHAT WE'VE BEEN TALK ABOUT IN IN
TERM
TERMLY SO NOW PROMISES YET BUT
WE'LL BE DEVELOPING A VOICE OF
FOUNDATION MODELS AND
TASK-SPECIFIC MODELS AND THAT
OUR INTENTION IS TO BE RELEASING
SOME FOR PUBLIC USE ON THE
GOOGLE SERVERS.
>> I RECOGNIZE A LOT OF IS
PROPRIETARY.
>> AS FOR THE DATA ITSELF, I
DON'T THINK SO.
IF YOU THINK ABOUT SORT OF WHAT
MAKES A.I. WORK IT'S THE DATA.
IT'S ALL ABOUT THE DATA.
THAT'S FRANKLY A HUGE
COMPETITIVE ADVANTAGE FOR GINKO.
THE MODELS THEMSELVES I THINK WE
WILL.
IF YOU THINK HAVING A TRAINED
MODEL IT'S LIKE YOU DON'T NEED
THE DATA ANY MORE.
I WANT TO USE THE NEW MODEL WITH
GOOGLE'S HELP TO DESIGN MY NEW
PROTEIN AND YOU JUST NEED THE
MODEL.
>> THANK YOU.
J OKAY.
WE'RE GOING TO WRAP UP THIS
MORNING'S TALKS WITH THE
EDUCATIONAL OPPORTUNITIES
AVAILABLE FROM THE FOUNDATION
FOR THE ADVANCED EDUCATION IN
SCIENCES FROM DR. MINDY MARIS.
>> GOOD MORNING, EVERYBODY.
I KNOW I'M PROBABLY THE ONLY
THING STANDING BETWEEN YOU AND
LUNCH SO I WILL TRY TO KEEP
THESE REMARKS VERY BRIEF.
AS ONE OF THE SPONSORS OF THIS
CONFERENCE, WE'RE VERY PLEASED
AT THE FOUNDATION FOR ADVANCE
EDUCATION IN THE SCIENCE TO HELP
SPONSOR THIS CONFERENCE AND I
REALLY APPRECIATE THE
OPPORTUNITY TO TELL YOU A LITTLE
BIT ABOUT WHO WE ARE AND WHAT WE
OFFER THAT MIGHT BE HELPFUL TO
THE ADVANCEMENT OF YOUR CAREERS
OR OF THE TRAINEES YOU HAVE IN
YOUR LABS.
SO FOR THOSE WHO MAY NOT KNOW
ABOUT OUR ORGANIZATION.
THE FOUNDATION FOR ADVANCED
EDUCATION IN THE SCIENCES WAS
FOUNDED OVER 60 YEARS AGO BY A
GROUP OF NIH SCIENTISTS WHO
ESSENTIALLY WANTED TO CREATE A
UNIVERSITY-LIKE ENTITY.
BASICALLY THEY WANTED
OPPORTUNITIES TO TEACH AND TO
LEARN.
AND SO WE ARE AN INDEPENDENT
NON-PROFIT ORGANIZATION LOCATED
ON THE BETHESDA CAMPUS ON THE
NIH IN BUILDING 10 IN THE
CLINICAL CENTER SO FEEL FREE TO
STOP BY AND SAY HI AND WE WORK
WITH THE NIH IN SEEKING AND
APPLYING FUNDAMENTAL KNOWLEDGE
ON THE BIOMEDICAL SCIENCE.
WE OFFER CREDIT-INITIATIVES AND
NON-CREDIT INITIATIVES IN
SUBJECT AREAS THAT COMPLIMENT
THE RESEARCH AND CAREER
DEVELOPMENT OF THE NIH COMMUNITY
AS WELL AS THE BROADER BIO
MEDICAL COMMUNITY.
AND SO THAT'S PROBABLY ONE KEY
POINT HOPEFULLY OUR PROGRAMS ARE
LOCATED TO THOSE ONLINE AND
THEY'RE HIGHLY ACCESSIBLE AND
FLEXIBLE NO MATTER WHERE YOU'RE
LOCATED OR WHAT TIME ZONE YOU'RE
IN.
AND SO AS I MENTIONED BRIEFLY ON
THE PREVIOUS SLIDE OUR ACADEMIC
INITIATIVES CAN BE BROADLY
DIVIDED INTO TWO CATEGORIES.
OUR NON-CREDIT INITIATIVES WE
REFER TO AS WORKSHOPS AND
ACADEMIC COURSES WHICH ARE
CREDIT-BEARING.
I'LL TELL YOU MORE ABOUT THE
FORMAT AND BENEFITS AND WHO
THESE ARE BEST SUITED FOR ON THE
FOLLOWING SLIDE BUT ESSENTIALLY
MOST OF OUR WORKSHOPS ARE
OFFERED IN A LIVE SYNCHRONOUS
FORMAT THOUGH FULLY ONLINE AND
THESE TEND TO BE HELD EITHER
OVER TWO TO FIVE CONSECUTIVE
DAYS OR SOMETIMES ONE TO TWO
SESSIONS OVER SEVERAL WEEKS.
OUR ACADEMIC COURSES THEY FOLLOW
AN ACADEMIC CALENDAR I'M SURE
ALL ARE FAMILIAR WITH FROM YOUR
TIME IN SCHOOL.
TYPICALLY SEVEN WEEKS LONG AND
TWO CREDITS.
WE'RE A NON-DEGREE GRANTING
ORGANIZATION BECAUSE THE
MAJORITY OF OUR LEARNERS ARE
ALREADY HIGHLY DEGREED.
HAVE YOU THE TERMINAL DEGREE IN
YOUR FIELD AND A WHOLE LOT OF
SCHOOLING BEHIND YOU.
WHAT WE OFFER ARE
MICROCREDE
MICROCREDENTIALS.
CAN DEMONSTRATE TO THE OUTSIDE
WORLD YOU GAINED A NEW BODY OF
KNOWLEDGE OR EXPERIENCE IN A
PARTICULAR FIELD.
WE FEEL LIKE THIS IS A WAY
THAT'S WELL ALIGNED WITH THE
NEEDS OF OUR LEARNERS TO
DEMONSTRATE THEY ACQUIRED THE
NEW KNOWLEDGE OR SKILL THAT
MIGHT HELP THEM GET THAT NEXT
GRANT OR NEXT JOB.
SO LET ME JUST TALK A LITTLE BIT
MORE ABOUT THE HIGHLIGHTS OF OUR
WORKSHOPS.
OUR WORKSHOPS ARE DESIGN TO
ALLOW THE LEARNERS TO VERY
RAPIDLY ACQUIRE NEW SKILLS OR
NEW KNOWLEDGE IMMEDIATELY
APPLICABLE TO THEIR RESEARCH OR
PROFESSIONAL NEEDS.
AS I MENTIONED BRIEFLY
PREVIOUSLY, THESE ARE TYPICALLY
LIVE LECTURES AND HANDS ON
PRACTICE SESSIONS HELD VIA ZOOM.
MOST ARE RECORDED SO DESIGN TO
BE HIGHLY FLEXIBLE IF YOU NEED
TO STEP AWAY TO DO A STEP IN
YOUR EXPERIMENT, DON'T WORRY,
YOU CAN ALWAYS COME BACK AND
VIEW THE LECTURE RECORDING.
AGAIN, AS I MENTIONED
PREVIOUSLY, THESE ARE TYPICALLY
HELD ON CONSECUTIVE WEEKDAYS BUT
WE HAVE SOME EVENING AND WEEKEND
AND WE OFFER CEUs AND
CERTIFICATES OF COMPLETION.
OUR ACADEMIC COURSES ARE OFFERED
IN AN ASYNCHRONOUS MODEL BUT NOT
SELF-P
SELF-PACED.
I'LL TALK ABOUT THAT AND THEY'RE
HIGHLY ACCESSIBLE OR FLEXIBLE
FOR BUSY PROFESSIONAL.
ALL OUR INITIATIVES ARE DESIGN
AROUND YOUR RESEARCH AND
PROFESSIONAL COMMITMENTS NOT THE
OTHER WAY AROUND.
TYPICALLY OUR ACADEMIC COURSES
ARE ORGANIZED EACH WEEK
CORRESPOND TO A MODULE AND
LEARNERS HAVE THE FREEDOM TO LOG
IN WHEN IT'S CONVENIENT AND
NAVIGATE FREELY WITHIN EACH
MODULE TO COMPLETE THEIR
LEARNING ASSIGNMENTS AND
INTERACT WITH THEIR TEACHER AND
OTHER PEERS IN THEIR CLASS AGAIN
ON A SCHEDULE CONVENIENT FOR
THEM.
TYPICALLY, THERE ARE NO REQUIRED
LIVE SESSIONS EXCEPT ENGLISH AND
SPANISH SESSIONS BECAUSE IT'S
IMPORTANT TO BE ABLE TO SPEAK TO
EACH OTHER AND TEACH EVER.
THOUGH OUR COURSES ARE ASY
ASYNCHRONOUS THEY'RE NOT
SELF-PACED AND THERE'S AN
INSTRUCTOR AND ENGAGED COMMUNITY
OF LEARNERS TO HELP WITH THE
PEER-TO-PEER LEARNING AND AIM TO
KEEP OUR STUDENT TO TEACHER
RATIOS LOW SO YOU CAN GET A HIGH
DEGREE OF PERSONALIZED
ATTENTION.
OUR AREAS OF STUDY CORRESPOND TO
THE NEEDS OF OUR COMMUNITY.
AS YOU CAN IMAGINE, IT'S THE
BIOMEDICAL SCIENCES, BIO
INFORMATICS AND DATA SCIENCE AND
STATISTICS AND TEST PREP, PUBLIC
POLICY, PROJECT MANAGEMENT AND
LEADERSHIP AS YOU CAN SEE HERE.
TO GIVE YOU A LITTLE BIT OF
INFORMATION ABOUT OUR ACADEMIC
TERMS, OUR WORKSHOPS ARE OFFERED
YEAR ROUND WHILE OUR COURSES
CORRESPOND TO A MORE ACADEMIC
CALENDAR YOU MAY BE FAMILIAR
WITH.
THERE ARE MORE DEFINED TIME WHEN
THOSE REGISTRATION PERIODS OPEN
FOR OUR COURSES BUT WE HAVE TWO
FALL AND TWO SPRING SESSIONS SO
LOTS OF OPPORTUNITIES TO GET
INVOLVED IN THE COURSES.
I JUST WANT TO HIGHLIGHT A
PROBLEM OF OUR INITIATIVES
RELEVANT TO YOU OR TRAINEES IN
YOUR LAB WE HAVE A MANUSCRIPT
CITING WORKSHOP THAT WALKS
THROUGH PREPARING, WRITING,
SENDING OFF A MANUSCRIPT AND
RESPOND.
THIS SAY HIGHLY SUPPORTIVE
ENVIRONMENT.
IF YOU HAVE TRAINEES IN YOUR
LABS WHO MIGHT BE AT THE EARLIER
STAGES OF DEVELOPING THAT
EXPERTISE AND MANUSCRIPTS THIS
MAY BE A GREAT OPTION TO GAIN
MORE EXPERIENCE AND A LOT OF
FEEDBACK IN HOW TO PRESENT THAT
DATA IN THE BEST POSSIBLE WAY.
AND WE OFFER THIS ONE EVERY
OTHER MONTH.
LOTS OF OPPORTUNITIES TO GET
INVOLVED.
APOLOGIES THERE'S A TYPO ON THE
SLIDE.
THESE ARE OUR 2024 SPRING
SEMESTER COURSES.
OUR REGISTRATION IS GETTING TO
LUNCH AT THE END OF NOVEMBER.
THESE ARE A SIM SAMPLING OF THE
OFFERING IN THE SPRING TERM AND
WILL OVER MORE THAN THIS BUT
LOTS OF CONTENT IN BIO
INFORMATICS, STATISTICS, OTHER
AREAS THAT MAY COMPLIMENT YOUR
RESEARCH.
HOPEFULLY BY NOW YOU'RE THINKING
HOW CAN I REGISTER AND GET THE
TRAINEES IN MY LABS TO REGISTER
FOR THOSE COURSES.
NAVIGATE OVER TO
EDUCATION.FAS.org AND YOU CAN
CREATE A LEARNER ACCOUNT AND
REGISTER.
WE DO WANT TO EMPHASIZE WHILE WE
TRY TO KEEP OUR TUITION
EXTREMELY LOW WE ALSO HAVE
SCHOLARSHIPS AVAILABLE FOR OUR
SELF-FUNDING STUDENTS.
IF YOU ARE FUNDING YOURSELF OR
IF SOME TRAINEES IN YOUR LABS
ARE FUNDING THEMSELVES WE
ENCOURAGE YOU TO TAKE ADVANTAGE
OF THE SCHOLARSHIP
OPPORTUNITIES.
WE DO OFFER A GOVERNMENT
DISCOUNT FOR ANYBODY FOR WHOM
THAT APPLIES BUT ALSO WANT TO
EXPAND OUR GOVERNMENT DISCOUNT
TO ALL OF YOU WHO MAY BE FROM
OTHER INSTITUTIONS.
SO WE'RE OPENING UP OUR
GOVERNMENT DISCOUNT TO ANYONE
WHO HAS ATTENDED TODAY.
SCAN THE QR CODE AND IT WILL
TAKE YOU TO A FORM TO REQUEST
THE DISCOUNT CODE TO GET THE
SAME RATE WHICH IS OUR LOWEST
RATE WE OFFER TO THE GOVERNMENT.
NOW, FINALLY, I ALSO WANTED TO
SHARE WE OFFER OPPORTUNITIES TO
TEACH AS WELL AS TO GAIN
TRAINING IN RESEARCH-BASED BEST
PRACTICES FOR TEACHING.
SO IF YOU WANT THE OPPORTUNITY
TO GET INTO ONE OF OUR ONLINE
CLASSROOMS, BUILD A COURSE AND
FACILITATE THAT LEARNING
EXPERIENCE FOR STUDENTS, WE
WOULD LOVE TO SPEAK WITH YOU
ABOUT THIS FURTHER.
SO AGAIN, PLEASE SIMPLY E-MAIL
US AT REGISTRAR@FAS.org AND TALK
ABOUT THE TRAINING AND SUPPORT
WE PROVIDE FOR FACULTY AND
VARIOUS TRAINING OPPORTUNITIES.
WE'RE SO HAPPY WE WERE ABLE TO
PROVIDE SOME SPONSORSHIP FOR
THIS MEETING AND APPRECIATE THE
OPPORTUNITY FOR ME TO SHARE WITH
YOU A LITTLE BIT ABOUT WHO FAS
IS AND WHAT SOME OF THE
RESOURCES WE CAN OFFER TO OUR
SCIENTISTS TO HELP ADVANCE YOUR
CAREER TO THE NEXT LEVEL.
PLEASE DON'T HESITATE TO GET IN
CONTACT AND DROP US AN E-MAIL OR
PHONE CALL BUT HOPE WE'LL BE
WELCOMING SOME OF YOU AND SOME
OF THOSE IN YOUR LAB IN OUR
WORKSHOPS OR PERHAPS AS A
FACULTY MEMBER.
I KNOW YOU'RE READY TO GO TO
LUNCH BUT ALSO HAPPY TO TAKE
QUESTIONS IF YOU HAVE SOME AND
THANK YOU AGAIN.
>> A QUICK QUESTION.
YOU MIGHT HAVE MENTIONED IT BUT
ARE THESE ALSO VIRTUAL COURSES
OR ALL IN PERSON?
>> CURRENTLY EVERYTHING IS FULLY
ONLINE.
HIGHLY ACCESSIBLE NO MATTER
WHERE YOU'RE LOCATED.
>> AMAZING.
THANK YOU.
>> ALL RIGHT SO MUCH.
ENJOY LUNCH.
>> THANK YOU VERY MUCH.
I'D LIKE TO CLOSE THE FIRST
MORNING SESSION.
LUNCH IS AVAILABLE UPSTAIRS TO
MY LEFT.
THE CAFETERIA IS OPEN.
THAT'S NEW.
THE CAFETERIA IS ONLY OPEN FOR
TODAY.
AND WE WILL SEE YOU AS WE GET
BACK AT 1:00.
ALL RIGHT, THANK YOU VERY MUCH.
I'D ALSO LIKE TO THANK ALL THE
SPEAKERS AND THE LIGHTNING TALK
PRESENTERS.
HOPE YOU HAD A GOOD LUNCH BREAK.
I'M CHIAYENG WANG I'LL BE YOUR
MODERATOR ON BIOMANUFACTURING
CASE STUDIES.
THIS AFTERNOON'S SESSION WILL
HAVE THREE TALKS IN THE MAIN
EVENT FOLLOWED BY A POSTER
QUESTION SOON AFTER WITHIN THE
MAIN EVENT.
AND WE WILL HAVE A 45-MINUTE
BREAK AFTER THE SECOND TALK.
THE THIRD TALK WILL START AT
2:45 TO PLEASE REMEMBER TO COME
BACK.
DURING THE BREAK, THIS IS MAINLY
FOR POSTER SETUP.
NOW, ORIGINALLY WE HAVE DR
DR. SOLOMON TO DO THE FIRST
LECTURE BUT SHE HAD DIFFICULTY
ARRIVING AT THE MAIN CAMPUS AND
ENCOUNTERED DIFFICULTY IN TERMS
OF THE ONLINE PRESENTATION SO
THE I.T. FOLKS ARE GOING TO
WORKING WITH HER SO WE'RE GOING
TO HAVE A SWITCH OF THE ORDER OF
PRESENTATION.
WE'LL START WITH THE LIGHTNING
TALK INSTEAD.
SO OUR LIGHTNING TALK WILL BE
GIVEN BY DR. MICHAEL MORASKIE A
Ph.D. CANDIDATE IN THE
DEPARTMENT OF BIOCHEMISTRY AND
MOLECULAR BIOLOGY FROM THE
UNIVERSITY OF MIAMI TALKING
ABOUT A PLATFORM FOR DETESTING
FORM SENSING MOLECULES KNOWN TO
BE PART OF CELL-CELL COMMUNITY
MECHANISM.
>> ALL RIGHT.
HELLO EVERYONE.
MY NAME IS MICHAEL MORASKIE AND
HERE TO PRESENT BY WORK
ILLUMINATING QUORUM FOR THE
NOVEL CORE SENSING MOLECULE DPO
AND REVELATIONS FROM THE
QUANTIFIED PRESENCE IN HUMANS,
ANIMALS AND BACTERIA.
SO THROUGHOUT MY Ph.D. JOURNEY
I'VE COME TO LEARN A LOT ABOUT
BACTERIAL COMMUNICATION AND
WITHIN THIS WORLD OF BACTERIAL
COMMUNICATION WE SORT OF THINK
ABOUT BACTERIA ENGAGING IN
BACTERIAL BEHAVIORS ALMOST AND
SPECIFICALLY TWO KINDS.
ONE BEHAVIOR TYPE OR I GUESS
GENETIC PROGRAMMING IN WHICH
THEY TAKE ON INDIVIDUAL
BEHAVIORS AT LOW CELL DENSITY.
PART OF THE GENETIC PROGRAMMING
DURING THE GENETIC EXPRESSION IS
THE SYNTHESIS AND RELEASE OF
SMALL CHEMICAL SIGNALLING
MOLECULES THAT DIFFUSE INTO THE
MICROENVIRONMENT.
YOU CAN IMAGINE AS THE BACTERIA
BEGIN TO DIVIDE AND GROW, THE
CONCENTRATION OF THE MOLECULES
BEGINS TO INCREASE IN THE
MICROENVIRONMENT.
THIS SORT OF TRIGGERS A SWITCH
INTO A GROUP SORT OF BEHAVIOR OR
GENETIC PROGRAMMING AND
BACTERIA.
SO IN ESSENCE THE CELLS ARE
USING THE SMALL CHEMICAL
MOLECULE KNOWN AS INDUCERS AS A
PROXY FOR CELL NUMBER.
THROUGHOUT THE YEARS AS QUORUM
SENSING HAS BEEN STUDIED MORE
AND MORE IT'S BEEN FOUND IT
TYPICALLY REGULATES BACTERIAL
BEHAVIORS WITH RELIANCE ON THE
SYNCHRONIZED EXPRESSION OF
GENETIC CIRCUITRIES.
IT WAS ORIGINALLY DISCOVERED IN
MARINE BIBLIOSPECIES USED TO
ILLUMENESS AND YOU'D WANT TO
INITIATE THESE BEHAVIORS ONCE
YOU HAVE ENOUGH.
AS WE ALL KNOW, BACTERIAL ARE
RARELY ISOLATED.
THEY'RE CONSTANTLY SURROUNDED BY
OTHER MICROORGANISMS.
IT TURNS OUT THERE'S BEEN
DIFFERENT CLASSES OF THESE AUTO
INDUCERS DISCOVERED THAT
REGULATE DIFFERENT SORTS OF
GROUP BEHAVIORS.
SOME AUTO INDUCERS ARE USED FOR
INTERSPECIES COMMUNICATION.
OTHERS HAVE BEEN FOUND USED FOR
INTERGENUS SPECIES AND
INTERKINGDOM AND THAT'S A
FASCINATING ANGLE TO THIS ALL
RECENTLY.
THERE'S A LOT OF WORK LOOKING
INTO VIRAL SPINE OF BACTERIAL
COMMUNICATION, ESSENTIALLY USING
THE AUTO INDUCERS TO NUMBER
THEIR LICENSE MISOGYNY DECISIONS
AND THE BACTERIAL LANGUAGES THEY
EMPLOY.
SO IN THE DONNER LAB WHICH I'M A
PART OF HAS LONG BEEN INTERESTED
IN STUDYING THE MICROB BBMICROB.
THE FIELD HAS EXPLODED RECENTLY
AND HAVE INCREDIBLE INSIGHT INTO
HOW MUCH IT REALLY AFFECTS OUR
OVER ALL HEALTH.
BUT THE CURRENT STATE OF THE
FIELD IS LARGELY CORRELATIONAL
IN NATURE AND THERE'S A
RECOGNITION THERE NEEDS TO BE
MORE MECHANISTIC INVESTIGATION
INTO HOW THE MICROBIOME
INFLUENCES OUR HEALTH.
AND THE DONNER LAB IS INTERESTED
IN LOOKING AT IT THROUGH THE
LENS OF QUORUM SENSING AND
STULYING THE DIFFERENT AUTO
INDUCERS OR DIFFERENT
COMMUNICATION SIGNALS.
SPECIFICALLY BECAUSE WE
UNDERSTAND THAT THESE SMALL
CHEMICAL MOLECULES TRIGGER
COMMUNITY-WIDE BEHAVIORS WHICH
MAY EXPLAIN CHANGES IN MICROBIAL
THE MAKE UP OF THE MICROBIOME
COMMUNITIES AND THE QUORUM
SENSING OF IT ALL THIS IS AN
OVER SIMPLIFIED VERSION GROUND
BACTERIA HAVE A SIMPLE CORE
MECHANISM AND THEY GENERALLY
HAVE RECEPTOR AND MOLECULE THAT
WILL BIND TO THE AUTO INDUCER
AND UPON THAT RECOGNITION IT IN
TURN TURNS INTO TRANSCRIPTION
FACTOR WHICH BINDS TO PROMOTER
REGIONS FOR THE UP REGULATION OR
DOWN REGULATION OF TARGET GENES.
THE CIRCUIT LIKE NATURE OF THE
QUORUM-SENSING COMMUNICATION
SYSTEMS MAKES THEM QUITE
AMENABLE TO THE DEVELOPMENT OF
WHOLESALE BIOSENSORS.
IF PEOPLE AREN'T FAMILIAR IT
CONSISTS OF ENGINEERED
MICROORGANISMS WHICH ARE
MODIFIED TO PRODUCE A FOREIGN
PROTEIN WHICH BINDS TO AN ANO
LYTE OF INTEREST AND THIS RELIES
ON THE RECOGNITION OF THE
REGULATORY PROTEIN TO THE A
ANOLYTE AND ON TOP OF THAT THE
THERE'S A REPORTER AGENT UNDER
THE TRANSCRIPTIONAL CONTROL OF A
PROMOTER REGION WHICH THE
PROTEIN CAN UPLETTING OR DOWN
REGULATE THE SYSTEM.
AND PIVOTING TO MY WORK IN THE
LAB AND THE DONNER LAB HAS A
WHOLESALE OF SENSORS FOR AUTO
INDUCERS AND THERE WAS A PAPER
PUBLISHED BY BONNIE BASS LEADING
THE CHARGE IN THE QUORUM SENSING
WORK AND IDENTIFIED A NOVEL
QUORUM SENSING MOLECULE IN THIS
TYPE OF CHOLERA AND WHAT IS
SPECIFIC ABOUT THIS CIRCUITRY
AND THE TOOL IS A PYRAZINE
MOLECULE BUT HAS BIOLOGICAL
ROLE.
AND IN BIBLIOCHOLERA IT'S BEEN
SHOWN TO INDUCE BUT IN THIS CASE
IT INHIBITS AND THE THOUGHT
CHOLERA BEING A PATHOGENIC
BACTERIA AND THE END GOAL IS TO
BE RELEASED BACK IN THE
ENVIRONMENT.
IT'S BELIEVED IT EVOLVED THE
MECHANISM TO KNOW WE
SUCCESSFULLY COLONIZED AND DONE
OR THING SO LET'S GET BACK OUT
THERE.
AND THE EXACT BIO SYNTHETIC
BATHE OF DPO WAS NOT UNDERSTAND
BUT IT'S AN AMINO ACID AND THE
HYDROGENASE WAS ALSO A KEY
ENZYME FOR ITS SYNTHESIS AND
THAT'S IMPORTANT DOWN STREAM
BECAUSE THE HYDROGENASE IS A
HIGHLY CONSERVED ENZYME
INDICATING OTHER BACTERIA MAY BE
EMPLOYING THIS QUORUM SENSING
MOLECULE FOR THEIR OWN PURPOSES.
ANOTHER THING TO MENTION IS THAT
IN THE CONTEXT OF THE
MICROBIOME, THREONINE INHABITS
THE GUT SO FURTHER SUPPORTING
THE POSSIBILITY THIS DPO MAY BE
IMPORTANT IN OTHER BACTERIAL
SPECIES.
SO YEAH, THIS PAPER WAS
PUBLISHED AND WE WERE INTERESTED
IN DEVELOP WHOLESALE BIO SENSOR
TO STUDY THIS MOLECULE
SPECIFICALLY.
YOU CAN SEE THE CIRCUIT CONSISTS
OF DPO AND BINDS TO THE PROTEIN
VQMA TO BIND TO SPECIFIC
PROMOTER REGION FOR A SILENCING
RNA AND INHIBITS THE TRANSLATION
OF THE TRANSCRIPTION FACTOR FOR
THE FORMATION OF GENES.
DPO FUNCTIONS TO INHIBIT
FORMATION IN BIBLIOCHOLERA.
WE HAD ALL THE INFORMATION WE
NEEDED TO TRY AND DEVELOP A
WHOLESALE BIOSENSOR.
WE HAD OUR ANALYTE OF INTEREST
AND THE PROMOTER REGION TO WHICH
THE PROTEIN BOUND UPON BINDING
DPO.
SO A LOT OF WORK WENT INTO
TAKING THESE INDIVIDUAL
COMPONENTS FROM THE VIBRIO
CHOLERAE AND THE WAY IT WORKS I
TOOK THE VQMA PROTEIN PLACED IT
UNDER THE CONTROL OF THE
CONSTITUENT PROMOTER AND THEN
TOOK A BIO LUMINESCENT CASSETTE
AND PLACED IT UNDER CONTROL OF
THE PROMOTER WHICH IS WHAT THE
COMPLEX BINDS TO TO UP REGULATE.
IN ESSENCE AFTER A LOT OF ASSAY
OPTIMIZATION WHICH INCLUDED
FIGURING OUT THE CORRECT OPTICAL
DENSITY AND INCUBATION TIMES AND
WHATNOT WE WERE ABLE TO DEVELOP
A WHOLESALE BIO SENSOR TO
QUANTIFY THE PRESENCE OF DPO
BASED ON A BIOLUMINESCENT SIGNAL
AND THERE'S WORK I'M NOT SHOWING
ON SHOWING SPECIFICITY.
I'LL HAVE A POSTER LATER IF
ANYONE IS CURIOUS IS THAT AND A
LOT OF WORK WENT INTO CHARACTER
INTO DETECT THE DPO.
THE NEXT PHASE SHOWED IT COULD
BE AN INTERESTING TOOL TO STUDY
THE MOLECULE.
AND RESPONSE CURVES ARE
GENERATED BY COMMERCIALLY
ACQUIRED DPO.
SO I TOOK SPENT MEDIA FROM
VIBRIO CHOLERA AND THE PEOPLE
WHO DISCOVERED THIS MOLECULE HAD
INDICATED E. COLI POSSIBLY MADE
IT AS WELL.
AND THEY KNOCK OUT A STRAIN OF
TDH BECAUSE IT'S THE KEY ENZYME
BORE THE SYNTHESIS.
TO SHOW WE CAN DETECT IN VITRO
AND BY CHOLERA AND E. COLI.
THE NEXT PHASE OF WORK WENT INTO
GIVEN OUR INTEREST IN STUDYING
THE MICROBIOME IN THE CONTEXT OF
THE MICROBIOME WE WANTED TO SEE
IF WE CAN DETECT THIS MOLECULE
IN STOOL.
KNOWING IT HAD BEEN DBO WAS USED
BY OTHER GRAM NEGATIVE BACTERIA.
A LOT OF WORK WENT INTO
DEVELOPING SAMPLE PREPARATION
PROTOCOL.
BEING A LIVING SENSOR WE'RE
LIMITED TO HAVING THE SENSOR BE
HAPPY, OF COURSE.
WE TOOK STOOL FROM WILD TYPE AND
GERM-FREE MICE AND THERE'S A
SPECTRUM IN WILD TYPE MICE AND
WE HAVE LITTLE TO NO SIGNAL FROM
THE SENSOR.
THEREFORE SUPPORTING THE IDEA
THAT THIS IS A BACTERIALLY
DERIVED MOLECULE PRESENT IN THE
GUT.
WE NEXT MOVED ON TO OBVIOUSLY WE
CONDITION SEE IN THE WILD TYPE
MICE STOOL AND WONDERING IF WE
CAN SEE IT IN HUMAN TOOL.
AND THIS IS SHOWING YES, WE CAN
IN FACT DETECT THIS MOLECULE IN
STOOL.
SO THIS WAS PRETTY EXCITING.
SOME OTHER WORK WENT INTO -- WE
HAVE SOME WORK LOOKING INTO THE
ENVIRONMENT ANALYSIS OF
QUORUM-SENSING MOLECULE I'M NOT
SHOWING HERE AND ALL TO SAY THIS
WORK WAS RECENTLY PUBLISHED BACK
IN JUNE AND CURRENTLY MY WORK IS
FOCUSSING ON TAKING THIS BIO
SENSOR AND LOOKING SPECIFICALLY
AT BACTERIAL STRAINS COMMONLY
ASSOCIATED WITH TO THE
MICROBIOME.
THAT'S BEEN A LOT OF MY WORK
CURRENTLY.
WE'RE ALSO INTERESTED IN THE --
THE DONNER LAB HAS BEEN
INTERESTED IN QUORUM SENSING
MOLECULE AS POTENTIAL BIOMARKERS
OF CROHN'S DISEASE OR EVEN
CANCER.
WE'RE ALSO LOOKING TO EMPLOYEE
THE SENSOR AND FINALLY WE'RE
LOOKING TO BUILD A TOOL KIT OF
BIO SENSORS AS MORE MOLECULE
DISCOVERED.
WE CAN START LOOKING AT AUTO
INDUCER FINGERPRINTS OF
MICROBIAL COMMUNITIES.
SO WITH THAT, I'LL FINISH AND
THANK YOU FOR THE NIH FOR HAVING
ME AND THANK YOU TO THE DONNER
DALE GROUP WHERE I'M ONE OF MANY
IN THE LAB.
AND SHAMELESSLY PLUG THE FACT
I'M AIMING TO DEFEND IN MAY.
MORE THAN HAPPY TO CONNECT.
WITH THAT I'LL TAKE ANY
QUESTIONS.
>> I'LL ASK A COUPLE
QUESTIONS -- A BIT OF NAIVE
QUESTIONS.
FOR THE WHOLESALE BIO SENSOR, TO
WHAT DEGREE DOES THE SYSTEM
DIFFERENTIATE VERY CLOSE SIMILAR
MOLECULES BUT ARE DIFFERENT?
>> EXCELLENT QUESTION.
IN MY POSTER, I TESTED A BUNCH
OF BPO AN LOGS AND IT TURNS OUT
THEY HAVE NO -- THE SENSOR
DOESN'T DETECT THEM.
OBVIOUSLY IT DEPENDS ON THE
REGULATORY PROTEIN YOU'RE
EMPLOYING.
IF IT'S PROMISCUOUS IT CAN BIND
TO OTHER THINGS AND THAT IN TURN
CAN BIND TO THE PROMOTER YOU'RE
USING.
YOU CAN IN FACT GET A FAULT
READING AND WE TESTED MOLECULES
AND DIDN'T GET ANY EFFECT.
THE CHOLERA IS SPECIFICALLY
DETECTING DPO SO WE ADOPTED THAT
FROM THE GENOME AND ANOTHER
ANGLE TO THAT QUESTION IS THIS
INTERKINGDOM SIGNALLING AND WE
FOUND SEROTONIN ACTUALLY
TRIGGERED A BIOLUMINESCENT
SIGNAL BASED ON THE CIRCUITRY OF
PSEUDOMONAS.
>> ANY SECOND QUESTION AND THIS
IS A SENSING APPROACH.
CAN IT BE USED TO IDENTIFY
EUKARYOTIC MOLECULES MAYBE
INTERFERING THAT ACTIVATE OR
INHIBIT BACTERIAL SIGNALLING.
>> DEFINITELY, YES.
THE ANGLE I WAS PITCHING WAS
MORE DPO SPECIFIC BUT WE HAVE A
NEW Ph.D. STUDENT IN THE LAB
DOING THAT AND TESTING HORMONES,
ENDOGENOUS COMPOUNDS AND BECAUSE
IT WAS FROM VIBRIO CHOLERA THERE
MAY BE APPROACHES THAT AFFECT
THE CIRCUIT.
>> THANK YOU.
>> SO IF YOU'RE -- YOU HAVE THIS
SYSTEM THAT IS DEVELOPING VPO, I
BELIEVE.
MAYBE YOU COVERED THIS BUT
WONDERING IF YOU HAVE ANY PLANS
FOR ESSENTIALLY REWIRING THE
SYSTEM TO USE THE SAME CIRCUITRY
EXCEPT TO DETECT SOMETHING ELSE
IN ORDER TO PRODUCE A DIFFERENT
RESPONSE AND CHANGE NEG --
CHANGING THE INPUT AND OUTPUT IN
GENERAL.
>> THAT'S A WHOLE OTHER FIELD OF
QUORUM SENSING WORK LOOKING INTO
ESSENTIA
ESSENTIALLY AND NOT BE ABLE TO
RECOGNIZE INITIATE VIRULENCE AND
USING ALTERNATIVES INSTEAD OF
ANTIBIOTICS.
>> THANK YOU.
>> YOU GOT IT.
THANK YOU, EVERYONE.
>> OKAY.
SO WE'RE ALL SET FOR -- OKAY,
FOR DR. RACHELLE SOLOMON'S
LECTURE AND SHE'S GOING TO GIVE
IT ONLINE.
SHE IS A SENIOR INVESTIGATOR OF
THE METABOLIC EPIDEMIOLOGY
BRANCH IN THE DIVISION OF CANCER
EPIDEMIOLOGY AND GENETICS AT THE
NATIONAL CANCER INSTITUTE AND
SHE WILL TELL US ABOUT THE BIO
MANUFACTURING AT THE FREDERICK
NATIONAL LABORATORY.
>> GOOD AFTERNOON.
ALL RIGHT.
SO THANK YOU IS THERE SOME
FEEDBACK OR IS THIS OKAY?
>> OKAY.
>> GREAT.
GOOD AFTERNOON.
THANK YOU VERY MUCH FOR THE
INTRODUCTION DR. WANG AND I'M
GRATEFUL TO THE ORGANIZERS FOR
INVITING ME TO SHARE WHAT OUR
GROUP IS DOING IN FREDERICK TO
ADVANCE CANCER CELL THERAPY.
WHAT WE'RE DOING AND WHAT I'M
GOING TO TALK ABOUT TODAY IS THE
WORK WE ARE DOING TO TACKLE
HURDLES OF MANUFACTURING
ENGINEERED T CELLS FOR PATIENTS.
OKAY.
SO FOR THOSE WHO ARE NOT
FAMILIAR WITH THE FREDERICK
NATIONAL LABS FOR CANCER
RESEARCH OR ALSO CALLED SNLCR,
THESE ARE FEDERALLY FUNDED
RESEARCH AND IT'S A FEDERALLY
FUNDED RESEARCH AND DEVELOPMENT
CENTER SUPPORTED PRIMARILY BY
NCI.
THEY WERE ORIGINALLY FOUNDED IN
1972 AND LOTS OF CHANGES HAVE
OCCURRED.
THE CURRENT CONTRACTOR WHO IS
STAFFING IS LITUS MEDICAL
RESEARCH INCORPORATED.
AND WHAT THE FNLCR RESPONDS
QUICKLY TO QUICK LY TO
CHALLENGES.
I WON'T GO INTO EVERYTHING
THAT'S GOING ON IN FREDERICK
BECAUSE THERE'S SO MUCH WORK I
ENCOURAGE YOU TO GO TO
FREDERICK.CANCER.gov TO LEARN
MORE ABOUT THE WORK GOING ON
THERE AND THE SERVICES.
SO WHAT I'M GOING TO TALK ABOUT
IS THE BIOPHARMACEUTICAL PROGRAM
FUNDED BY NCI.
IN PARTICULAR BY THE DIVISION OF
CANCER DIAGNOSIS AND IT'S LED BY
JIM DOROWSHOW AND THIS
MANUFACTURING RESOURCE IS
OVERSEEN BY THE DEVELOPMENTAL
THERAPEUTICS PROGRAM AND THE
GROUP I'M IN CALLED THE
BIOLOGICAL RESOURCES BRANCH OR
BRB WHICH IS LED BY DR. JASON
YOVANDICH WE HAVE THE TASK OF
OVERSEEING THE WORKSHOP IS DONE
AT THE BIOPHARMACEUTICAL
DEVELOPMENT PROGRAM.
SO ON THE NEXT SLIDE WHAT I AM
SHOWING AGAIN IS THAT THESE
UNIQUE RESOURCES AT FREDERICK
HAS COMPLEXITY THEY'RE FUNDED BY
NCI.
THE OPERATION OF THE BDP PROGRAM
ITSELF IS THAT IT IS STAFFED AND
MANAGED BY CONTRACTORS FROM
LEIDOS AND UNIQUELY LOCATED AT
FREDERICK AT THE FNLCR.
THEIR MISSION SO NOVEL
THERAPEUTICS OF TREATMENT OF
CANCER AND OTHER DISEASE.
THIS IS BY PROVIDING
MANUFACTURING, PROCESS DEVELOP.
PROCESS ANALYTICS AND QUALITY
ASSURANCE CAPABILITIES AND
EXPERTISE.
THEY'VE DEVELOPED FIRST IN CLASS
PRODUCTS AND THINGS THAT HAVE
COMPLEX REGULATORY CHALLENGES
AND OFTEN SELECTED.
IF WE GO TO THE NEXT SLIDE YOU
CAN SEE HIGHLIGHTS OF THE
CAPABILITIES OF THE BDP AND
THOSE ARE PROCESS DEVELOPMENT
GMP MANUFACTURING CAPABILITIES
AND TESTING AND RELEASE OF
BIOLOGICS.
WE HAVE A VERY STRONG PROCESS
ANALYTICS AND QUALITY CONTROL
PROGRAM WHICH IS CRITICAL IN
DEVELOPING ASSAYS AND TESTING OF
THE BIOLOGIC PRODUCTS.
AND THEN WE ALSO HAVE QUALITY
ASSURANCE OVERSIGHT WHICH REALLY
IS CRITICAL BECAUSE THIS ENSURES
GMP COMPLIANCE AND THE OVER ALL
QUALITY OF THE SYSTEMS AND THE
PRODUCTS THAT WE PRODUCE.
ALONG WITH THAT WE HAVE GREAT
REGULATORY AFFAIRS SUPPORT WHICH
HELP IN THE FILING OF THESE
NOVEL DRUGS FOR I.N.D.s FOR
CLINICAL TRIALS.
BDP DOES COMPLY WITH FDA
REGULATIONS AND STANDARDS
INCLUDING THE 21CFR CODES.
SO WHAT DO WE PRODUCE THERE?
WE PRODUCE ALL TYPES OF
BIOLOGICS FOR EXAMPLE,
MONOCLONAL ANTIBODIES,
RECOMBINANT PROTEINS AND VIRAL
AND DNA VACCINES, PEPTIDES AND
GENE THERAPY PRODUCTS.
AND WHAT I'M TALKING ABOUT TODAY
IN PARTICULAR IS AN AREA WE JUST
CAME INTO A FEW YEARS AGO WHY IS
IS THE PRODUCTION OF CELL-BASED
PRODUCTS.
ONE INTERESTING THING TO NOTE
FOR FOLKS INTERESTED IN LOOKING
INTO THE BDP IF YOU GO TO THE
FREDERICK WEBSITE YOU CAN SEE
LINKS DIRECTLY TO THE BDP BUT
PROVIDE MANY SERVICES INCLUDING
GMP TRAINING OF STAFF AND ALSO
FOR OTHER AGENCIES AND HAVE ALSO
BEEN OPPOSED AS THE TRAINING
SITE FOR SO WE HAVE A UNIQUE
PROCESS IN THAT ALL OF THE SOPs
THAT THE BDP HAS ARE MADE
PUBLICLY AVAILABLE.
IF YOU GO TO THE WEBSITE YOU'LL
BE ABLE TO SEE SOPs THAT CAN
POTENTIALLY HELP YOUR WORK.
ORE THE YEARS THE BDP HAS
MANUFACTU
MANUFACTURED MANY LOTS OF OVER
100 DIFFERENT PRODUCT HAVE GONE
TO CLINICAL TRIALS AND I THINK
THERE ARE TWO PRODUCTS THAT HAVE
BEEN LICENSED BUT THAT IS NOT
OUR AREA.
WE ARE NOT TRYING TO LICENSE
PRODUCTS.
WE ARE SIMPLY TRYING TO BRIDGE
THAT GAP TO GET PRODUCTS TO THE
CLINIC.
AND SO, YOU'LL SEE THE NCI IS
FOCUSSED ON SUPPORTING PRODUCT
DEVELOPMENT.
IN PARTICULAR, THIS IS ONE OF
THE REASONS WHY RESOURCES LIKE
THE BDP ARE AVAILABLE.
AS YOU KNOW MANY IN OUR AUDIENCE
ARE FROM BASIC RESEARCH
LABORATORIES AND SOME ARE
FURTHER DOWN THE TRANSLATIONAL
PIPELINE.
BUT WE KNOW THAT PRODUCT
DEVELOPMENT CAN BE VERY
CHALLENGING IN THAT IT REALLY
REQUIRES A PARADIGM SHIFT TO
ADVANCE A PRODUCT FROM THE BENCH
TO THE CLINIC.
THAT IS DONE BY A CHANGE IN MIND
SET WHERE YOU'RE GOING FROM
BASIC RESEARCH HYPOTHESIS DRIVEN
TO A PARADIGM IN WHICH YOU'RE
ENGINEERING A PRODUCT WITH THE
END IN MIND.
AND THE END BEING GETTING TO THE
CLINIC AND GETTING TO THE
PATIENTS.
AND WHAT WE FIND IS THAT
RESOURCES LIKE THE BDP ARE VERY
USEFUL IN THAT PRODUCT
DEVELOPMENT PATHWAY.
AND SO IF WE LOOK ON THE NEXT
SLIDE THIS IS SOMETHING THAT
MANY OF YOU MAY BE FAMILIAR WITH
WHICH IS THAT THE PATHWAY TO THE
CLINIC IS CHALLENGING AND THAT'S
WHERE THE EXPERTISE OF THE BDP
AND OTHER RESOURCES ARE REALLY
IMPORTANT BECAUSE WE OFTEN HAVE
AN EXPECTATION THE PATH IS
STRAIGHTFORWARD AND LINEAR AND
INVESTIGATORS MAY COME IN AND
SAY I KNOW WHAT I WANT TO DO TO
GET THIS ANTIBODY TO THE CLINIC
AND THERE'S MANY CHEMICALS IN
BIOMANUFACTURING SO IT'S
CHALLENGING BUT FORTUNATE LY FO
RESOURCE IS TO HELP IN THE
PROCESS.
AND I WAS EXCITED TO PARTICIPATE
IN THIS MEETING BECAUSE WHAT WE
ARE SEEING IS THAT AND WHAT I'VE
APPRECIATED FROM THE PREVIOUS
TALKS AND WHAT THE ORGANIZERS
PUT TOGETHER IS THE SYNTHETIC
BIOLOGY AND PRODUCT MESH WELL
TOGETHER AND HAVE THIS OVERLAP
WHERE WE KNOW PRODUCT
DEVELOPMENT INVOLVES ENGINEERING
OF A QUALITY PRODUCT THE
MANUFACTURING PROCESS TO ENSURE
YOU CONSISTENTLY GET A HIGH
QUALITY PRODUCTION OF YOUR
PRODUCT.
SIMILARLY SYNTHETIC BIOLOGY SAY
FIELD IN WHICH AIMS TO ENGINEER
MOLECULES AND CELLS AND
ORGANISMS WITH NEW FUNCTIONS.
THE KEY IS THE ENGINEERING MIND
SET AND WHAT NCI DID WAS
LEVERAGE THE PRODUCT DEVELOPMENT
EXPERTISE THAT HAS BEEN AT THE
BDP MANY YEARS AND USE THAT TO
ADDRESS THESE NEW MANUFACTURING
HURDLES THAT COME UP BECAUSE OF
SYNTHETIC BIOLOGY.
IN PARTICULAR WHAT I'M TALKING
ABOUT HERE IS MANUFACTURING OF
ENGINEERED CELLS FOR PATIENTS.
WE ENTERED THE FEEL BY FIRST
GOING -- WORKING TOWARDS MAKING
ENGINEERED CHIMERIC ANTIGEN
RECEPTORS OR CARS FOR T CELLS
AND THOSE RECEPTORS WILL ALLOW A
T CELL TO TARGET AN ANTIGEN,
BECOME ACTIVATED AND ALSO BECOME
ELIMINATED.
THIS IS A PROCESS WHERE IT'S A
UNIQUE MANUFACTURING PARADIGM
WHERE YOU ARE KIND OF IN A RACE
TO TAKE THE STARTING MATERIAL
WHICH IS THE PATIENT'S AFOREESE
-- AND GET THEM BACK TO THE
PATIENT IS IN NEED OF THE CELLS.
AND WE WERE LOOKING AT PRODUCT
DEVELOPMENT AND SYNTHETIC
BIOLOGY ENERGYING TO ADDRESS
MANUFACTURING CARS.
WHAT WE SEE IS AGAIN WE
LEVERAGED THE EXPERIENCED STAFF
AND THE EXISTING CGMP
MANUFACTURING FACILITIES AND
PROCESSES AND PUT IN PLACE PUT
IN PLACE A CLOSED AND AUTOMATED
MANUFACTURING SYSTEMS THAT COULD
MAKE THESE AND WERE ABLE TO PUT
IN PLACE PROCESS VALIDATIONS,
ASSAY DEVELOPMENT AND WHICH IS
VERY IMPORTANT TO LOOK AT THE
QUALITY OF THE PRODUCTS THAT
YOU'RE PRODUCING THIS HAS BEEN
LACKING IN THE CELL THERAPY
FIELD IN THAT IT'S CHALLENGING
TO A CONSISTENT QUALITY.
SOMETIMES THESE WERE BEING DONE
IN SMALL ACADEMIC CENTERS OR
EVEN LARGE ONES BUT IN
FACILITIES THAT WEREN'T
NECESSARILY EXPERIENCED IN THE
HIGH QUALITY PROCESSES
ASSOCIATED WITH GMP.
WE WERE ABLE TO PUT IN PLACE
SYSTEMS TO DO RAPID PRODUCT
RELEASE AND GETTING THEM BACK TO
THE PATIENT VERY IMPORTANT.
WE WERE ABLE TO LOOK AT THE
LOGISTICS THAT ARE COMPLEX AND
ASSOCIATED WITH PUTTING THOSE IN
PLACE SO WE WOULD BE ABLE TO
SUPPORT THING SUCH AS MULTI-SITE
CLINICAL TRIALS.
SOME SITES COULD BE FAR A PART
AND WHILE IT WOULD PRODUCE A
QUALITY PRODUCT WE HAD TO ENSURE
IT GETS TO EACH SITE IN THE SAME
QUALITY WHICH IS DIFFERENT
COMPARISON TO CENTERS THAT ARE
LOCALLY MANUFACTURING JUST FROM
THEIR CLINICAL TRIAL.
PUTTING IN PLACE QUALITY SYSTEMS
AND THINGS LIKE HAVING TO TEST
THE CRYO FREEZING OF THE CAR T
CELLS AND HOW WE STANDARDIZE ALL
THOSE THINGS.
IT'S BEEN A LOT OF WORK AND
EFFORT TO BE ABLE TO LEVERAGE
THE PRODUCT DEVELOPMENT
EXPERTISE WE HAD AND PUT IT
TOWARDS ENGINEERING SITE
THERAPY.
THIS IS ONE OF THE CLINICAL
TRIALS WE'RE CURRENTLY
SUPPORTING.
WE HAVE MANUFACTURED PRODUCTS
FOR FOUR DIFFERENT DOSE LEVELS
AND THIS IS TO GENERATE CAR T
CELLS DIRECTED TO THE CD33
ANTIGEN FOR CHILDREN AND YOUNG
ADULTS WITH ACUTE MYELOID
LEUKEMIA AND THIS TRIAL BEING
SPONSORED BY NNDP THE STUDY IS
BEING LED BY AND YOU CAN SEE WE
HAVE WITH THE CENTRAL
MANUFACTURING CAPABILITY, WE'VE
BEEN ABLE TO MANUFACTURER
PRODUCTS FOR PATIENTS ACROSS
SICH DIFFERENT CLINICAL SITES.
YOU CAN SEE HERE FROM SEATTLE AN
CHILDREN IN COLORADO TO BOSTON
AND CHOP AND SOME PATIENTS AT
NCI ALSO.
AND THE RESULTS WILL BE
PRESENTED IN DECEMBER AT THE ASH
ANNUAL MEETING AND I INVITE YOU
ALL TO LOOK FOR THE RESULTS
COMING SOON.
THIS UNIQUE SITUATION WE'RE IN
AND GET TO HEAR FROM THE
CLINICAL P.I.s, THE IMPACT THESE
PRODUCTS ARE HAVING ON THEIR
PATIENTS.
WE'RE ALSO MANUFACTURING CAR T
CELLS FOR ANOTHER CLINICAL
TRIAL.
THE GD2 CAR FOR TRIAL AND DOING
CENTRALIZED MANUFACTURING FOR
THIS AND SEVERAL PATIENTS HAVE
ALSO BEEN DOSED FOR THIS TRIAL
WANT TO BRING YOU TO THE NEXT
SLIDE WHERE WITH THE TWO TRIALS
WE'RE CURRENTLY ACTIVELY
MANUFACTURING PRODUCT FOR THOSE,
WE ARE ALSO LEVERAGING OUR
ABILITY TO DEVELOP PROCESSES AND
BRING SOME OTHER CANDIDATES TO
TRIAL.
HERE'S MANY PROJECTS THAT COME
TO US THROUGH DIFFERENT
MECHANISMS BUT PRIMARILY THROUGH
THE NEXT EXPERIMENTAL
THERAPEUTICS PROGRAM.
WE'RE ABLE TO MANUFACTURE AND
DEVELOP PROCESS TO DEVELOP CAR T
CELLS OR OTHER PRODUCTS RELATED.
SO THE VIRUSES THAT ARE USED TO
DO THE GENETIC ENGINEERING.
AND I PROMISE TO KEEP THE TEAM
ON TIME SO I'M GOING TO GO TO
THE NEXT SLIDE.
WHAT I WANT TO SAY IS THERE'S
MANY MANUFACTURING HURDLES
AHEAD.
WE'RE TRYING TO ADDRESS THOSE
AND WHAT WE'RE HOPING TO DO IS
INCREASE CAPACITY AND ONE OF THE
WAYS IS BY COMMISSIONING GMP
MANUFACTURING SUITE FOR THE WORK
AND WORKING ON OTHER
MANUFACTURING PLATFORMS AND
TECHNOLOGY.
WE EXPECT THERE'S BEEN A LOT OF
DEVELOPMENT WORK THAT HAS GONE
INTO MAKING A PROCESS THAT IS
SCALABLE FOR CRISPR-BASED CELL
THERAPY PRODUCTS.
NOT JUST RETROVIRUSES.
AND ANOTHER TECHNOLOGY THAT
WE'RE INTRODUCING IS ALSO THE
IPFCs WHICH MAY BE VALUABLE IN
MAKING MORE ALLOGENEIC PRODUCTS.
I'D LIKE TO GO TO THE NEXT SLIDE
AND TRYING TO END HERE AC WE'RE
KEEPING THE PATIENTS IN MIND AND
THIS HAS BEEN WHY WE ARE DOING
THE WORK WE DO.
AND THIS SUMMER WE WERE ABLE
TO -- WE WERE FORTUNATE TO HAVE
PATIENT FAMILIES VISIT US AND
ONE OF THE VISITORS WAS ACTUALLY
A FORMER PEDIATRIC PATIENT THAT
WAS TREATED ON CD19 CAR T CELL
TRIAL AND SO WE'RE LOOKING --
THIS SOUR GUIDE AND WE'RE HOPING
TO BRING THE MANUFACTURING
EXPERTISE TO SOLVE THESE
PROBLEMS RELATED WITH THE
MANUFACTURER OF ENGINEERED CAR T
CELLS.
THESE ARE SOME OF THE FOLKS WE
WANT TO ACKNOWLEDGE AND WE HAVE
THE CONTACT INFORMATION AND IF
YOU WANT TO KNOW MORE HOW TO
ACCESS THE RESOURCES AT THE
FREDERICK LABS FOR MANUFACTURING
CELLS THE INFORMATION IS MOSTLY
ONLINE THROUGH THE NCI
EXPERIMENTAL THERAPEUTICS
PROGRAM AND THE LINK IS PROVIDED
HERE OR YOU CAN REQUEST A
CONSULTATION WITH THE PRODUCT
DEVELOPMENT STAFF IN DCTD AND
WILL CONSULT WITH YOU AND TALK
ABOUT THE MANUFACTURING HURDLES
OR DEVELOPMENT PROCESS OR
STRATEGIES THAT YOU ARE FACING
WITH YOUR OWN SYNTHETIC
BIOLOGICAL CANDIDATE.
AND THANK YOU FOR YOUR ATTENTION
AND IF THERE'S ANY QUESTIONS
FEEL FREE TO REACH OUT TO ME.
THANK YOU.
>> THANK YOU, DR. SOLOMON.
CAN YOU SAY ONLINE FOR A LITTLE
BIT AND LET ME SEE IF THERE'S
ANY QUESTIONS FROM THE AUDIENCE.
QUESTIONS?
THANK YOU VERY MUCH.
MAYBE LET ME JUST ASK ONE QUICK
QUESTION.
SO DOES FREDERICK LABORATORY
ONLY MANUFACTURE MATERIAL THAT
IS FOR CANCER?
-- CANCER RESEARCH?
>> LIMITED FOR CANCER DISEASE OR
DOES IT ALSO MANUFACTURE
MATERIALS FOR OTHER DISEASES?
>> THAT'S A GREAT QUESTION.
WE'RE PRIMARILY FUNDED BY NCI SO
MANY OF OUR PRODUCTS ARE FOR
CANCER INDICATIONS BUT WE DO
ALSO SUPPORT SOME PRODUCTS FOR
OTHER INDICATIONS.
WE HAVE SUPPORTED WORK FOR
EXTRAMURAL INVESTIGATORS AND
INTRAMURAL INVESTIGATES FROM
OTHER INSTITUTES LIKE NYE NAIAD
AND INFECTIOUS DISEASE AND SO
MUCH.
>> THANK YOU VERY MUCH,
DR. SOLOMON.
>> THANK YOU FOR STAYING WITH US
AND BEING PATIENT WITH US.
SO WE'RE GOING TO TAKE A BREAK
AND PLEASE COME BACK HERE AT
2:45 OR OUR THIRD AND FINAL
PRESENTATION.
LET'S RESUME THE SESSION.
WE'LL HAVE OUR THIRD
PRESENTATION OF THE LAST
SPEAKER.
THE SPEAKER IS DR. ARIEL
WEINBERGER THE CEO AND
CO-FOUNDER OF AUTO NOM US
THERAPEUTICS FOCUSSING ON
ARTIFICIAL IMMUNE SYSTEMS THAT
WORK AGAINST INFECTIOUS DISEASES
AND CANCER.
HE'S GOING TO GIVE US AN UPDATE
ON SOME OF THEIR WORK.
>> SORRY, ABOUT THAT, GUYS.
THANK YOU, CHIAYENG FOR THE
INTRODUCTION AND TO JEMONT AND
THE NIBIB TEAM FOR HAVING US.
I'M ARIEL WEINBERGER THE CEO OF
AUTONOMOUS THERAPEUTICS.
I'M HERE WITH TIM NODDEN OUR CSO
IN THE FRONT YOU'LL SEE HIM IN A
MOMENT AS THIS LOADS UP.
HOPEFULLY I CAN MAKE THIS
HAPPEN.
I'M ARIEL WEINBERGER THE CEO OF
AUTONOMOUS THERAPEUTICS AND OUR
CSO WILL COUPLE FOR QUESTIONS.
YOU SEE PICTURES OF US ON THE
SCREEN.
WE'RE A COMPANY BASED CLOSE TO
HERE DOWN ROCKVILLE PIKE IN
ROCKVILLE, MARYLAND.
TO FOCUS ON THE CORE OF THE
COMPANY TO BUILD ESSENTIALLY
NEXT GENERATION RNA AND USE
SYNTHETIC BIOLOGY TO CONTROL
WHEN PROTEINS ARE EXPRESSED.
IT'S USING SYNTHETIC BIOLOGY
TO -- I'M HAVING TROUBLE WITH
SLIDES TODAY, GUYS.
S I APOLOGIZE FOR THE INTRO.
THESE ARE PEOPLE IN THE COUNTRY
LOCATED CLOSEBY AND USE ATHLETIC
BETH WHERE AND WHERE THERAPEUTIC
PROTEINS ARE EXPRESSED AND THINK
OF IT AS USING RNA OR NUCLEIC
ACID TO BUILD PRECISION
MEDICINES THAT ONLY EXPRESS
PROTEINS AND ONLY TRANSLATE
PROTEINS IN DISEASE CELLS WHILE
AVOIDING CELLS YOU WANT TO SPARE
FROM EXOGENOUS PROTEIN
TRANSLATION.
TO GIVE YOU MOTIVATION AS TO WHY
YOU'D WANT TO DO THAT IT MAY BE
OBVIOUS BUT I'LL DO THIS
NONETHELESS, IF YOU THINK OF THE
STATE OF THE ART WHERE HE STAND
WITH NUCLEIC ACID VACCINES OR
SELF-AMPLIFYING RNAs OR CIRCULAR
RNAs THEY'RE ESSENTIALLY NOT
ABLE TO DISCRIMINATE HEALTHY AND
DISEASED CELLS OR ABLE TO HAVE
SPECIFIC PROTEIN TRANSLATION IF
YOU TAKE THE RNAs AND THEY'RE
ENCAPSULATED IN NANO PARTICLES
AND DELIVER TO PROTEIN WHAT YOU
MAY ENCODE IN THE mRNA VACCINE
WORKS WELL.
THEY'LL PRODUCE AS MANY CELLS
YOU MAY WANT TO AVOID AND
PRETEND YOU WANT TO GET INTO AN
ANTIGEN PRESENTING CELL BUT
PERHAPS WANT TO AVOID A NEURON,
FOR EXAMPLE.
WHATEVER IT IS YOU WANT TO AVOID
TENS TO BE THE CASE IN TERMS OF
THE CELL ENTRY MECHANISM
TARGETED AS A RESULT OF THAT,
YOU'RE ESSENTIALLY GOING HAVE
ANO GENIC PROTEIN WHERE IT COMES
INTO CONTACT.
IF I STEP BACK I SAID RNA AND
mRNA VACCINES ARE TARGETED IN
TERMS OF DELIVERY AND YOU'RE
SAYING THAT'S KIND OF A DUMB
PROBLEM BECAUSE WE KNOW THEY'RE
SUCCESSFUL OVER THE LAST THREE
AND A HALF YEARS AND WHY I MATE
BE A PROBLEM TO CONSIDER IS
VACCINE HAVE A REAL ADVANTAGE
OVER THERAPEUTICS.
DON'T NEED A HIGH DOSE FOR THE
VACCINE TO BE EFFECTIVE IF
YOU'RE THINKING ABOUT LIKE TO
THE COVID VACCINE AS THE 30 TO
40 MICROGRAMS AND THAT'S ENOUGH
TO HAVE INCREDIBLE PROTECTIVITY
AND HAVE THE IMMUNE SYSTEM TO
ACT AS AN AMPLIFIER.
WHAT IF YOU WANTED TO DELIVER A
THERAPEUTIC PROTEIN, HORMONE,
ENZYME, ENZYME REPLACEMENT
THERAPY IN IF YOU WANT TO DO
THAT YOU HAVE TO TREAT EVERY
CELL.
AND ON AVERAGE THE DOSE REQUIRED
FOR mRNA YOU'RE TALKING THE
MILLIGRAM RANGE.
AND MANY CLINICAL TRIALS IS A
CRISPR CAS AND mRNA THAT ENCODES
A CAS PROTEIN AND HAVE DOSES UP
TO 75 MILLIGRAMS.
NOT MICROGRAMS BUT MILLIGRAMS
AND NOW I GET IN THE PROBLEM OF
POTENTIALLY YOU COULD HAVE
PROTECTIVE PROTEINS WHETHER
HORMONES LIKE INSULIN AND LIFE
SAVING BUT CAN YOU CONTROL THAT
AND LIMIT THE OFF TARGET PROTEIN
EXPRESSION TO LIMIT AND MAXIMIZE
THE THERAPEUTIC WINDOW?
THERE'S TWO PRINCIPLED WAYS.
ONE IS TO LIMIT WHERE THE mRNA
GOES.
YOU CAN MAKE BETTER LIPID NANO
PARTICLES BY WHICH THEY AVOIDED
OWNER CELLS AND BY CONSTRUCTION
THE mRNA GETS INTO SUBSET OF
CELLS AND YOU CAN DO THE MATH IN
YOUR HEAD AND PROTEIN WILL ONLY
BE MADE IN THE CELLS RNA GETS
INTO.
SEEMS LIKE ONE SOLUTION
PRESUMING YOU HAVE A CELL
SURFACE MARKER THAT
DIFFERENTIATES HEALTHY AND
TARGET FROM OFF-TARGET.
IN THE WAY YOU DON'T WANT TO USE
THE LMP TO DO THE DISCRIMINATORY
DECISION YOU CAN MAKE THE
DECISION AND HAVE THE DATE AS IT
WERE OCCUR LATER IN THE PROCESS.
YOU CAN HAVE AN LNP LIKE YOUR
LNP FOR VACCINES GETS INTO EVERY
CELL NEARLY EQUIVALENTLY AND NO
TARGET AT THE LEVEL OF ENTRY BUT
ONCE IT GETS INTO CELLS THE RNA
IT INJECTS AND DELIVERS IT'S
SMART AS IT WERE OR AUTONOMOUS
IN THE SENSE OF BEING ABLE TO
SENSE THE INTRACELL DEVELOPMENT
AND DETERMINE OR DECIDE WHETHER
OR NOT TO MAKE PROTEIN WHETHER
IT'S A DISEASED OR NOT DISEASED
CELL AND EITHER WAY YOU CUT IT
YOU HAVE THE SAME OUTPUT AT THE
END OF THE DAY IN TERMS OF
PRINCIPLES IN LIMITING TARGETING
PROTEIN EXPRESSION TO THE CELLS
YOU HOPEFULLY WANT TO TARGET
WHETHER YOU MAKE THE GATE POST
ENTRY AT THE LEVEL OF
TRANSLATION VIA RNA IS CALLED
SMART FOR LACK OF A BETTER TERM
AND GATE AT THE POINT OF ENTRY
THE IMPROVED LIPID NANO
PARTICLE.
I SET UP THIS DIFFERENT METHOD
DOING THINGS AND AND WE WON'T DO
IT AT THE NANO MART CAL AND EEL
USE WHAT YOU MIGHT SCHAFSHG OF
AS OFF THE CELL LIPID NANO
PARTICLE WITH THE VACCINE AND
WITH THE STANDARD LIPID NANO
PARTICLE WITH NO CAPABILITY OF
DISCRIMINATING CELL TYPE WE CAN
STILL HAVE THE DISCRIMINATION
OCCUR BY VIRTUE OF A MOLECULE BY
SMART RNA AND YOU'RE PROBABLY
WONDERING IF THAT'S POSSIBLE AND
HOW YOU COULD DO THAT.
TO GET TO THAT POINT, YOU
CERTAINLY COULDN'T USE YOUR OFF
HE SHELF STANDARD RNA TECHNOLOGY
OR mRNA OR ANOTHER
SELF-AMPLIFYING RNA.
THOSE TECHNOLOGIES ARE
ESSENTIALLY AND HAVE THE SAME
KIND OF INFORMATION THEY PROVIDE
THE SAME INFORMATION TO THE
RIBOSOME WHETHER A CELL IS
HEALTHY FOR IF IT WERE INFECTED
WITH A VIRUS.
THE FIRST HALF OF THE TALK GOING
FOR THE NEXT 20, 30 MINUTES I'LL
SHOW THE CASE OF VIRUSES.
I'M GOING TO WANT TO PRODUCE A
PROTEIN IN DISEASE CELLS AND
CELLS INFECTED WITH A TARGETED
VIRUS AND WANT TO PRODUCE NO
PROTEIN AND WANT TO BE SILENT
TRANSLATIONALLY OR LACKING VIRUS
AND FOR mRNA HEALTHY OR VIRUS
INFECTED THE mRNA WOULD PROVIDE
THE SAME AS THE TEMPLATE FOR
MAKING PROTEIN.
WHAT IF I CAN MAKE A NEW CLASS
OF RNA THAT WAS ESSENTIALLY A
LOCK ENCRYPTED BY ENCRYPTED FROM
THE RIBOSOME.
HIDDEN TRANSLATIONALLY AND
IMMUNOLOGICALLY SO THE SILENCE
MEANT IN THE ABSENCE OF A
SPECIFIC INTRACELLULAR TRIGGER
OR TARGET IN THIS CASE A VIRAL
INFECTION, THAT ENCRYPTED VIRAL
INFECTION IS OFF.
NO PROTEIN'S COMING OUT OF THERE
BUT IF YOU INFECT THE CELLS YOU
TREAT WITH THE ENCRYPTED RNA
WITH A TARGETED VIRUS IT WILL
ACTIVATE AND PRODUCE LARGE
AMOUNTS OF WHATEVER PROTEIN YOU
ENCODE.
IT'S IMPORTANT TO NOTE I'M AND
PLUG AND PLAY SYSTEM AND PUT
WHENEVER PROTEIN YOU WANT INTO
THE ENCRYPTED RNA CHASIS AND
I'VE SHOWN A LOT OF CARTOONS AND
NOT A HECK OF A LOT OF DATA AND
WE'LL BUILD AN ENCRYPTED RNA AND
MAKE PROTEIN FOR INFLUENZA NOT
PROTEIN.
YOU GET THE ENCRYPTED RNA INTO
HUMAN LUNG CELLS DIDN'T REALLY
MATTER AND IN THE ABSENCE OF
INFLUENZA WE'RE LOOKING AT
PROTEIN PRODUCTION FROM THE
ENCRYPTED RNA.
YOU SEE BASELINE LEVELS, NEG
LEGIBLE AND YOU DON'T GET 2 OR
10X TIMES PROTEIN BUT MASSIVE
AMOUNTS FIVE LOGS HERE AND
PROBABLY SAYING, WELL, THAT
DOESN'T PROVE SENSITIVITY TO THE
CONTEXT OR PRESENCE OF VIRAL
TARGET DOESN'T PROVE IT'S
SENSING THE VIRUS PER SE.
AND THE CELL GETS AGITATED
PROPRODUCES IMMUNE PROTEINS AND
THE ENCRYPTED RNA TURNS ON AND
IF I INFECT IT WITH VIRAL TARGET
OR PATHOGEN TO TRIGGER AN INNATE
IMMUNE RESPONSE US MAY BE
TALKING ABOUT, YOU WON'T HAVE
THAT ACTIVATION OF THE ENCRYPTED
RNA AND ONLY TURN ON FOR
INFLUENZA AND BE DEAD AS A DUCK
FOR CORONAVIRUS OR IN THIS CASE
ANY EMCV.
I'VE GIVEN THE SENSITIVITY AND
SPECIFICITY HOW MUCH IT TURNS ON
FOR INFLUENZA BUT WHAT I HAVEN'T
ANSWERED IS THE DOUBLE ED-EDGED
SWORD OF THE SPECIFICITY IF IT
DETECTS AND TRIGGERS WHATEVER
PROTEIN YOU ENCODE WHAT THE PAY
LOAD IS YOU'RE PROBABLY SAYING
VIRUSES MUTATE AND YOU'LL
ESSENTIALLY HAVE A TARGET NO
LONGER SENSED AND A USEFUL
TECHNOLOGY FOR AN RNA VIRUS FOR
INFLUENZA AND IT'S NOT.
WE'LL KEEP THE ENCRYPTED VIRUS
THE SAME BUT START VARYING THE
VIRUS.
AND SAME ENCRYPTED RNA AND SAME
SEQUENCE LOOK WHAT HAPPENS.
IT TURNS ON.
NOW YOU HAVE PAN INFLUENZA A AND
AN EXAMPLE FROM H1N1 AND THE
BRANCHS OF THE INFLUENZA FAMILY.
THE IT WORKS WITH INFLUENZA B
WHICH IS COOL BECAUSE IT GIVES
THE NOTION YOU MAY HAVE THE
BEGINNING OF A PAN INFLUENZA
TECHNOLOGY WHICH IS NOT THE CASE
FOR STATE OF THE ART VACCINES.
READ THE BYLINE AT THE BOTTOM.
IT'S NOT JUST AN OFF AND ON OR
BINARY EFFECT BUT IF YOU VARY
THE AMOUNT OF INFLUENZA YOU
PROVIDE THE TARGET YOU PROVIDE,
YOU'D SEE THE MONOTONICALLY
INCREASING AMOUNT OF PROTEIN
PRODUCTION OF ACTIVATED OF THE
ENCRYPTED RNA AND THREE
DIFFERENT ENCRYPTED V1, V2,V3
AND WHEN DEVELOPED OVER TIME
THEY GOT BETTER AND YOU CAN SEE
AND INFLUENZA VIRUS LOW MOIs OF
1 IN 1,000 CELLS AND NOVEL NEWER
VERSIONS ARE EXTREMELY
RESPONSIVE.
THE SENSOR IS SENSITIVE AND
ACTIVATES TO HIGH LEVELS AND
KEEPS INCREASING MONOTONICALLY
AS YOU INCREASE THE TARGET IN
THE CELLS FOR THE ENCRYPTED RNA.
THE OTHER WAY TO THINK OF IT IS
BECAUSE DIFFERENT INDIVIDUALS
HAVE DIFFERENT LEVELS OF VIRUS
AND YOU'LL HAVE PATIENT-SPECIFIC
DOSES IF YOU WERE TO PUT
THERAPEUTIC PROTEIN BASED ON THE
PATIENT-SPECIFIC LEVELS THE
AMOUNT OF TARGET IN EACH.
YOU ARE STARTING TO THINK,
GREAT, I CAN DETECT INFLUENZA
BUT IS THIS FOR ONE VIRUS.
TURNS OUT NOT.
THIS IS RSV AND WE MAKE AN
ENCRYPTED RNA AND NOW WE TARGET
RSV.
AND YOU HAVE THE SAME EFFECT
ALONG THE X AXIS AND LOOKING AT
DIFFERENT RSV VARIANTS AND RSV
As AND Bs AND BASELINE LEVELS OF
ENCRYPTED PROTEIN LEVEL IN THE
PRESENCE OF RSV THREE AND FOUR
LOGS ABOVE BACKGROUND AND SAME
DYNAMIC FOR INFLUENZA.
IF YOU USE THE SAME ENCRYPTED
RNA IT'S OFF.
IT'S SPECIFIC TO RSV BUT PAN
RSV.
GUESS WHAT, YOU CAN DO THE SAME
FOR SARS COV2 AND SENSE THE
PATTERN AND MAKE AN VARIANT
WHETHER THE ALPHA, BETA, DELTA,
MOUSE-ADAPTED OMICRON AND
VARIANTS ALONG THE X AXIS AND IF
YOU TAKE A PROTEIN COMING OUT OF
THE ENCRYPTED RNA.
TO REMIND YOU IN CASE I WENT
QUICKLY, THE Y AXIS SHOWS THE
ENCODED PROTEIN IN THAT
ENCRYPTED mRNA CHASIS.
IT ONLY ACTIVATES IN THE CONTEXT
OF SARS COV2 IF IT'S ENCRYPTED
RNA AND DO IT FOR BIO THREATS AS
WELL.
SAME GAME BUT CAN TAKE A SINGLE
ENCRYPTED RNA AND TURN IT ON TO
HIGH LEVELS IN THE PRESENCE OF
THE VIRUS AND IN THE ABSENCE
IT'S SILENT AND OFF.
I CAN SHOW YOU WE BUILT THESE
CRYPTED mRNAs FOR A SLEW OF
VIRUSES.
AND OTHER VIRUSES HERE.
WE'VE DONE IT FOR HPV AND A SLEW
OF VIRUSES WE'VE DONE THIS FOR.
I WENT QUICKLY BUT WHAT I TRIED
TO SHOW YOU WE CAN BUILD
ESSENTIALLY A CENSOR -- SENSOR
WILL ACTIVATE TO PRODUCE THE
PROTEIN ENCODED AND THE ABSENCE
OFF THE TARGET IS
TRANSLATIONALLY SILENCED BUT
HAVEN'T SHOWN THERAPEUTIC IMPACT
OR RELEVANCE TO THE BEGINNING OF
THE TALK WHICH WAS COULD WE
BUILD RNA SENSOR ACTUATORS THAT
DETERMINE WHERE AND WHERE
THEY'RE EXPRESSED.
THAT'S THE NEXT PART OF THE
TALK.
INSTEAD OF A REPORTER PROTEIN
AND PUT A THERAPEUTIC PROTEIN
YOU PROBABLY WANT TO KNOW IF IT
WILL HAVE ADVOCACY AND WHAT I
MEAN BY THAT IS WILL IT RESPOND
TO THE VIRAL TARGET OR WHATEVER
TARGET YOU PROVIDE IT WITH
QUICKLY ENOUGH TO PRODUCE ENOUGH
THERAPEUTIC PROTEIN TO QUASH AN
ACUTE INFECTION.
MAKING A LOT OF PROTEIN ISN'T
EQUIVALENT TO QUASH AN INFECTION
THERE'S SPEED AND RATE PRESENT
IN THERAPEUTIC CASE AND LESS
PRESENT IN THE REPORTER CASE YOU
SAW.
FIRST I HAVE TO CHOOSE WHICH
THERAPEUTIC PROTEIN TO PUT IN.
I CAN PUT WHATEVER PROTEIN --
APOLOGIZE FOR MY FACILITY OF THE
MIC, PUT ANY PROTEIN YOU WANT
INTO AN ENCRYPTED CHASSIS AND
USE THE SAME PROTEIN FOR
DIFFERENT ENCRYPTED mRNAs BUT
CHOOSE WHATEVER PROTEIN YOU
WANT.
THIS IS NOT RELEVANT TO THE
ENCRYPTED mRNA CHASSIS AND THIS
IS A PROTEIN THAT ESSENTIALLY
SAY HOST-ACTING IMMUNOMODULE TRY
PROTEIN AND mRNA SO IT'S NOT THE
FANCY STUFF.
YOU CAN TAKE THE ENTRIES ALONG
THE X VIRUS AND VIRUSES AND I'LL
SHOW ONE EXAMPLE THEY'RE ALL
BASICALLY THE SAME PATTERN TAKE
INFLUENZA A AND WHAT THE HEIGHT
OF THE BAR SHOWS ON THE Y AXIS
IS ESSENTIALLY THE LEVEL OF
KNOCK DOWN THAT THE PROTEIN OR
mRNA WHICH ENCODES THE
IMMUNOMO
IMMUNOMODULATORY PROTEIN MARKS
AND THE LNP ENCAPSULATE THE PRE
TEEN AND THE OTHER CULTURE
TREATED WITH THE GFP OR REPORTER
PROTEIN.
I'M CONTROLLING FOR THE
PRODUCTION PROCESS AND LNP.
I WANT TO SEE THE EFFECT OF THE
PROTEIN CONTROLLING AS MUCH AS I
CAN FOR THE BYSTANDER EFFECTS P
SYNTHESIS MAY CARRY WITH IT AND
YOU SEE FOUR OR FIVE LOGS OF
EFFICACY SOMETIMES WITH THE SAME
PROTEIN PAY LOAD.
I'LL TAKE THIS PROTEIN IF YOU
WANT TO THINK OF IT THAT WAY AND
ENCRYPT IT SO IT'S NOW GOING TO
BE BECOME VIRUS SPECIFIC AND YOU
SAW THE SAME ENCRYPTED RNA
WORKED FOR EVERY VARIANT OF SAY
SARS COV2 BUT DIDN'T TURN ON
WHEN INFLUENZA INFECTED THE
CELLS AND YOU SEE THE HOST mRNA
BUT PUTTING IT INTO AN ENCRYPTED
CHASSIS.
THIS IS A LONG MOUTHFUL FOR THE
ENCRYPTED mRNA WITH THE REPORTER
PROTEIN AND PUT IN THE
IMMUNOPROTEIN AND SEE IF IT'S
THERAPEUTIC AND THE EXPERIMENT
IN CELL CULTURE.
YOU TAKE CELLS AND TREAT THEM
WITH AT191 ENCODING THE
THERAPEUTIC PROTEIN IN BLUE OR
IN RED THE SAME WITH THE LAN AND
YOU PUT A NON-THERAPEUTIC A
REPORTER PROTEIN AND LUCIFERASE
AND YOU SEE THREE, FOUR LOGS
WORTH OF EFFICACY.
IF I DO THE SAME INFLUENZA AND
DON'T INFECT WITH SARS COV2 I
GOT NO DIFFERENCE BETWEEN SHAM
AND REPORTER VERSION AND AGAIN
THOUGH THE PROTEIN IS PAN VIRAL
IT'S ONLY GETTING ACTIVATED IN
THE CONTEXT OF SARS COV2 ON THE
LEFT AND BECAUSE THE PROTEIN
DOESN'T GET MADE AND NOT LEAKY
AND IT'S NOT INHERENTLY
IMMUNOGENIC IT'S NOT PROTECTIVE
AGAINST INFLUENZA.
AND YOU MAKE ENCRYPTED mRNAs AND
PUT THE SAME PROTEIN INTO THOSE
CHASSIS AND HERE YOU LOOK AT THE
ILLUSTRATIVELY AND LOOK AT RSV
WHICH A RED FLUORESCENT PROTEIN
EMBEDDED SO IT'S PRODUCING RFP
AND LOOK FAR LOST YOU SEE
PROTEIN AND IT'S REPLICATED
UNHINDERED AND UNTREATED CELLS.
IF YOU TREAT THEM WITH THE SHAM
ON THE FAR RIGHT THE ENCRYPTED
RNA AND NOT ENCODING A
THERAPEUTIC PROTEIN, NO AFFECT.
CHASSIS IS NOT A PROBLEM AND IF
YOU DO THE RIGHT ENCRYPTED RNA
THAT SENSES RSV BUT PRODUCES A
THERAPEUTIC PROTEIN CALLED AT225
AND IF YOU TAKE THE ENCRYPTED
RNA YOU SEE BASICALLY A BLACK
BOX IN ABSENCE OF RSV PRODUCED
RFP AND TO THE KNOCKDOWN IS TWO
LOG.
AND THERE'S A SPECIFICITY FOR A
GIVEN VIRAL FAMILY.
YOU'RE SAYING TO YOURSELF, WHAT
IF I WANTED IMMUNITY OR
PROTECTION AGAINST MULTIPLE
VIRAL FAMILIES THE WAY IS TO
BUILD COCKTAILS.
EACH IS INHERENT INDEPENDENT
SENSORS AND NO REASON YOU CAN'T
MAKE COCKTAILS OF INDEPENDENT
SENSORS.
HERE'S WHAT HAPPENS IF YOU
COMBINE THESE AND TREAT CELLS
WITH BOTH AND LOOK ON THE X
VIRUS AND NOR SARS OR COV2 OR
SEE PROTEIN EXPRESSION AND WITH
RSV ALONE THE RNA SHOOTS UP AND
THE ENCRYPTED RNA GOES OFF AND
INFECT WITH SARS COV2 YOU GET
THE PATTERN.
AND MAGICALLY IF YOU INFECT WITH
RSV AND CELLS TREATED YOU GET
BOTH ENCRYPTED RNAs PLAYING WELL
TOGETHER AND TURNING ON AND
RESPONSIVE TO THE MULTIPLE
CO-INFECTION CASE.
AND FOR THE EFFICACY AND
RESPONSIVENESS.
ONE POINT TO MAKE BEFORE WE GET
TO THE IN VIVO BECAUSE ENCRYPTED
RNAs ARE SET UP TO BE
ESSENTIALLY OFF TRANSLATIONALLY
SILENT TAILOR-MADE FOR
PROPHYLAXIS AND ONLY ACTIVATE IN
THE CONTEXT OF INFECTION AND
THINK THAT MAY BE DUMB BECAUSE
RNA IS LABIL AND IT'S NOT GOING
TO DO A HECK OF A LOT OF GOOD AS
A PROPHYLACTIC BECAUSE IT WILL
BE GONE BEFORE YOU'RE INFECTED
AND COULD WE MODIFY AND WE CAN
AND USING A TRICK FOR SAY SRNAs
AND SIMILAR.
THE EXPERIMENT IS TRIVIAL.
WITH WE HAVE THE ENCRYPTED RNA
AND THIS MODIFIED VERSION I'M
SHOWING IN I GUESS ORANGE.
IT'S NO ENCRYPTED RNA AND I'LL
TREAT THEM AT DAY ZERO AND DO
ANYTHING FOR TWO WEEKS.
NEVER RETREAT, TWO WEEKS LATER
I'LL INFECT WITH VIRUS
SPECIFICALLY RSV ENCRYPTED RNA
CASE.
TWO WEEKS LATER YOU INFECT AND
YOU'RE MEASURING DID THE
ENCRYPTED RNA STICK AROUND AND
DID IT STICK AROUND IN A ROBUST
ENOUGH WAY TO TURN ON IN THE
CONTEXT OF INFECTION AND
FUNCTIONALLY IS IT PRESENT AND
RESPONSIVE TWO WEEKS LATER?
IT HAS NO PROTEIN PRODUCTION AS
I SHOULDN'T.
THE ORIGINAL ONE IS LONG GONE
AND DOESN'T WORK AT DAY 14 BUT
DID AT ZERO AND MODIFIED WORKS
AT DAY 0 AND 14 AND IF THE
ABSENCE OF THE INFECTION DOESN'T
PRODUCE PROTEIN YOU INFECT WITH
RSV WITH THE PLUS AND THE
MODIFIED RSV CREN ENCRYPTED RNA
YOU CAN PROPHYLACTICALLY
ADMINISTER WEEKS IN ADVANCE.
A
AND YOU MAY SAY ENCRYPTED mRNA'S
ARE COOL FOR TWO, THREE WEEKS
BUT WHAT ABOUT MONTHS?
YOU HAVE A DNA THAT CAN MAKES ON
CON STITCHIVE LY EXPRESS THE DN
AND HAVE A STOP SIGN NO PROTEIN
UNLESS THE CELLS ARE INCORRECTED
WITH THE VIRUS AND DO THIS TO
RESPOND TO INFLUENZA AND WILL
ONLY EXPRESS PROTEIN IN
PRINCIPLE IF INFLUENZA IS THERE
TO ACTIVATE THE ENCRYPTED RNA
FROM THE DNA.
AND IT TREATS ONCE AT ZERO.
THAT'S THE ONLY TIME I TREAT THE
CELLS AND RUN AT THE CULTURE FOR
13 WEEKS AND MEASURE PROTEIN AND
I SEE THE BLEW BOX AT THE ORIGIN
OF THE Y AXIS WHICH IS GOOD
BECAUSE I DON'T WANT TO MAKE
PROTEIN IN THE ABSENCE OF VIRUS.
I KEEP INFECTING THE ALIQUOT.
IT'S PERSISTING AND RESPONSIVE
WEEKS LATER.
WE DID ONE MORE THING BEFORE I
GET TO THE COOL IN VIVO DATA.
WE TOOK THE CELLS AND DID TWO
PARALLEL STUDIES.
ONE WITH THE ENCRYPTED RNA AND
THE PARALLEL CULTURE WAS THE DNA
ENCODING AND ENCRYPTED DNA WITH
A REPORTER PROTEIN AND THE DNA
CASE UNTIL NOW AND INFECT WITH
INFLUENZA.
DON'T RETREAT.
I TREATED EACH CULTURE 13 WEEKS
AGO AND YOU SEE THE DIFFERENCE.
NOT ONLY IS IT PAN VARIANT,
VARIOUS ACTIVATED AND EFFECTIVE
IT'S PROPHYLACTICALLY INFECTED
WEEKS IN ADVANCE.
LET'S MAKE A RUN FOR THE IN VIVO
DATA.
SO YOU THINK ABOUT IN VIVO AND
WANT TO KNOW HOW YOU COULD TEST
ENCRYP
ENCRYPTED AND WE BUILT A NOVEL
LNP WITH THE COMMERCIALLY
AVAILABLE LNPs SYSTEMICALLY
DELIVERED WE BUILT AN LNP AND
RETRACTRY TO THE SHEER FORCE AN
NEBULIZER WOULD IMPART AND COULD
AFFECT THE DELIVERY OF THE LNP
AND BUILT ONE REFRACTORY TO THE
SHEER FORCE OF AN NEBULIZER AND
YOU CAN SELF-ADMINISTER.
ENCRYPTED OR ANY RNA USING THIS
LNP AS A DELIVERY VECTOR.
IT'S INHALABLE.
AND THE LEFT YOU'RE LOOKING AT
AND IT'S NOT EFFICACY BUT
ROBUSTNESS IS NOT AFFECTED BY
NEBULIZATION AND THE
DIFFERENCE -- TAKE THE NEBULIZED
LNP AND THE DIFFERS BETWEEN THE
GREEN AND BLUE CURVE.
THE GREEN IS THE SHAM AND THE
DIFFERENCE BETWEEN THOSE IS THE
DIFFERENCE DUE TO THE PRODUCTION
OF THE THERAPEUTIC PROTEIN AND
SAME DIFFERENTIAL BETWEEN GREEN
AND BLUE WHETHER YOU NEBULIZE
AND I CAN DO MORE THAN NEBULIZE
BUT OUT IT FOR AT-HOME STORAGE
AND PUT IT IN THE FRIDGE AND
WAITED FOUR MONTHS AND YOU SEE
THE SAME EFFECT.
AND WE HAVE LOW-END OFF TARGET
TISSUES THE LNP ISN'T REACHING
HERE.
YOU GET THE POINT.
YOU CAN LOOK AT -- THIS IS ALL
LOOKED AT BY A BOARD CERTIFIED
PATHOLOGIST AND TREATING MICE
AND ANIMALS WITH THE ENCRYPTED
LNP AND LOOKING LEFT AT
ESSENTIALLY MICROGRAPHS BY THE
BOARD CERTIFIED PATHOLOGIST AND
LOOK AT RENAL FUNCTION AND
CLINICAL BLOOD CHEMISTRY.
EVERYTHING LOOKS GOOD AND LOOK
AT ANIMALS INFECTED WITH SARS
COV2 AND LOOK AT THE ACTIVATED
LNP OR INFECTED ANIMAL THIS
ENCRYPTED RNA DOESN'T BECOME
TOXIC POST INHALATION.
I'M NO EXPERT ON THE MICROGRAPHS
BUT THE PATHOLOGIST SAYS THEY
LOOK GOOD.
WHAT ABOUT EFFICACY?
YOU TAKE A LETHAL MODEL OF SARS
COV2 A MOUSE-ADAPTED VIRUS AND
PASS IT FOR GENERATIONS IN A
MOUSE.
IN THIS CASE 30 GENERATIONS AND
A MODEL SET UP AND PERFORMED AT
THE STATE OF IOWA AND PASSAGE
FOR 30 GENERATIONS IS
ESSENTIALLY HIGHLY LETHAL SUCH
THAT IN THE ABSENCE OF EFFECTIVE
THERAPY THE MICE WILL HAVE TO BE
SACRIFICED OR IT'S ESSENTIALLY
DEAD, THE MICE THAT IS, IN SEVEN
TO 10 DAYS.
SEE THAT WHETHER YOU LOOK AT
SURVIVAL ON THE RIGHT OR LOOK AT
BODY WEIGHT ON THE LEFT IN ABOUT
IF YOU TAKE PBS AND INFECT THE
ANIMALS WITH AN INTRANASAL
CHALLENGE OF A 10LD50 AND TREAT
THEM WIN PBS AND THEY'LL DIE.
IF YOU TREAT THEM WITH WHAT WE
CALL AT19 LUC AND THE ACTIVATED
CHASSIS ENCODING A LUCIFERASE
THE CHASSIS THE RNA ITSELF THE
PRODUCTION PROCESS THE LNP NONE
OF THAT WILL CONJURE OR INFER
INFECTION AND IF YOU TREAT THEM
WITH THE BLUE THE A191 THAT
ENCODES THE THERAPEUTIC PROTEIN
THE MICE SURVIVE.
SO IT'S FOR ENCRYPTED RNA AND
NOTE YOU GIVE AN INHALABLE
ENOUGH TO PROTECT THE MICE IF
YOU TREAT 48 HOURS OR TWO DAYS
PRIOR TO INFECTION.
THE SAME RESULTS FROM THE LAST
SLIDE THE SINGLE PROPHYLACTIC
TREATMENT OR IF YOU TREAT AFTER.
AND I TREAT THE MICE WITH ONE
DOSE AND SAME RESULT, IT'S
PROTECTIVE WHEREAS THE SHAM IS
NOT PROTECTIVE AND I GUESS THE
CHASSIS ISN'T PROTECTIVE AND
NEED TO PRODUCE THE PROTEIN BUT
YOU COULD BE THINKS IT'S NOT
ACTIVATING IN VIVO IN TERMS OF
SARS COV2 INFECTION BUT LEAKING
THERAPEUTIC PROTEIN AND THAT
THERAPEUTIC PROTEIN IS
PROTECTIVE AND CON FEFERS AN IME
RESPONSE AND AND THAT IS NOT
PROTECTIVE AGAINST SARS COV2
WHILE IT IS PROTECTIVE AGAINST
RSVs AND IF WE SWITCH OUT THE
SENSOR OR SWITCH OUT THE
THERAPEUTIC EFFECTER YOU'LL OWE
ABLATE EFFICACY AND ON THE LEFT
YOU'RE LOOKING AT SAFETY AND
LOOKED AT BY A BOARD CERTIFIED
PATHOLOGIST AND ON THE RIGHT
VIRAL LOAD KNOCK DOWN WHETHER IN
THE NAVAL PHARYNX OR OTHER
TISSUES OF THE HAMSTER MODEL.
AND ONE WITH NON-VIRAL TARGETS.
I SHOWED IN VIVO DATA FOR SARS
COV2 BUT I DIDN'T SHOW YOU COULD
DO IT FOR OTHER VIRAL TARGETS.
IN THIS CASE INFLUENZA.
THE ANALOGOUS SYSTEM.
IT'S A LETHAL MOUSE MODEL WHERE
THE INFLUENZA IS A HIGHLY
VIRULENT INFLUENZA KILL THE MICE
IN SIX OR EIGHT DAYS IN THE
SYSTEM BUT IF YOU GIVE IT AT158
THE INFLUENZA ENCRYPTED RNA THEY
SURVIVE IF YOU WERE TO GIVE IT
THE SARS AT191 THE MICE WOULD
NOT SURVIVE.
DO IT FOR ANY VIRUS YOU'D LIKE
IN THE SAME MANNER.
THIS IS INHALABLE AND WE'VE
SHOWN YOU CAN TAKE A NOVEL RNA
ABSENT VIRUS ON TOP AND ABSENCE
OF A TARGETED VIRUS AND TARGETED
SEQUENCE OR PROTEIN WHATEVER
YOU'RE GOING AFTER DOESN'T
PRODUCE PROTEIN.
IT'S SILENT AND IMMUNE LOGICALLY
AND HIGHLY RESPONSIVE AND
SENSITIVE AND PRODUCES HIGH
LEVELS OF WHATEVER PROTEIN YOU
ENCODE NOTABLY THERAPEUTIC
PROTEINS AND TO WORK TOWARDS THE
ENDS OF THE TALK YOU'RE PROBABLY
SAYING THAT'S A COOL STORY BUT
IS IT RESTRICTED TO VIRUSES.
AND PRODUCE THERAPEUTIC PROTEINS
AND WHAT IF I WANTED TO MAKE
PRECISION CHEMO THERAPIES AND
HERE I'M LOOKING AT WHAT I
SHOWED YOU EARLIER BUT NOW WITH
A NON-VIRAL TARGET.
IT'S NOT FROM A VIRUS AND YOU
GET THE SAME EFFECT YOU SAW
EARLIER AND NOW NOT TO RECOGNIZE
THE VIRAL TARGET BUT TO
RECOGNIZE THE NON-VIRAL TARGET.
YOU CAN DO THIS IN A WAY THAT IS
ESSENTIALLY NON BINARY BUT
RESPONSIVE THAT HAS HIGH DYNAMIC
RANGE.
HERE I'M KEEPING THE SAME AMOUNT
OF ENCRYPTED mRNA ACROSS THE
RIGHT SIDE OF THE PICTURE AND
THE ENCRYPTED LEVEL DOESN'T
CHANGE.
ALL I DO IS CHANGE THE TARGET
LEVEL AS I INCREASE THE TARGET
LEVEL YOU SEE THIS MASSIVE
INCREASE IN THE PROTEIN
PRODUCTION FROM THE ENCRYPTED
RNA ESSENTIALLY YOU HAVE MORE
KEY OR ACTIVATION OR TARGET TO
ACTIVATE YOUR ENCRYPTED RNA.
HOPEFULLY I'VE GIVEN YOU A
PICTURE YOU CAN WORK OUTSIDE OF
VIRUSES.
ONE OTHER POINT ABOUT CANCER AND
SHOW FINAL DATA, CANCERS ARE
HAVE A SECOND CHALLENGE TO THEM
P
.
ON ONE HAND WE HAVE INTERESTING
TARGETS TO MAKE A
CANCER-SPECIFIC mRNA BUT YOU MAY
WANT TO TARGET MORE THAN ONE
SPECIFIC MUTATION OR SEQUENCE.
WHAT I MEAN BY THAT IS CANCERS
IN GENERAL TIPIFY NOT BY A
SINGLE MUTATION BUT
CONSTELLATION OF MULTIPLE
MUTATIONS.
THIS IS REAL DATA FROM PATIENTS
AND A COUPLE PAPERS FROM SCIENCE
AND NATURE AND BREAST CANCER
PATIENTS WITH METASTATIC BREAST
CANCERS IN COMPARISON TO HEALTHY
TISSUES WHERE YOU SEE LOOK AT
COLUMN A AND PATIENTS WITH NO
MUTATIONS IN A RANGE OF
ONCOGENES WHICH ARE ACTIVATING
ONCOGENES OR TUMOR SUPPRESSER
GENE AND LOSS OF MUTATION WOULD
BE TUMORIGENIC AND IF YOU LOOK
YOU HAVE NO MUTATIONS IN THE
HEALTHY TISSUE THAT'S WHAT THE
ENTRY BOX MEANS AND IF YOU LOOK
ACROSS SIX DIFFERENT PATIENTS, B
THROUGH G YOU SEE EACH HAS AT
LEAST TWO OR THREE THREE
MUTATIONS AND NOT A SINGLE ONO
GENIC MUTATION WITH THE
TRANSFORMATION.
WHAT I MIGHT BE INTERESTED IN
DOING IS HAVING ENCRYPTED RNA
THAT FUNCTIONS LIKE A GATE THAT
NOT ONLY TURNS ON A SINGLE
CANCER MUTATION IS PRESENT BUT
MULTIPLE ONES ARE THERE AND
UNLOCKING OF MULTIPLE LOCKS AT
EACH TUMOR MUTATION MIGHT LOCK,
ABSENCE ALL THOSE BEING THERE
THE ENCRYPTED mRNA IS OFF AND
YOU CAN MAKE N GATES.
HERE'S THE DATA.
YOU HAVE ANY ENCRYPTED TRAINED
TO ACTIVATE A FOUR DIFFERENT
SIGNALS HAVE TO BE PRESENT THE
COLORED IN ENTRY OF THE TABLE
MEANS THAT SIGNAL'S PROVIDED TO
CELLS AND YOU SEE ONLY THE FAR
RIGHT ONLY THE CASE WHERE I GIVE
ALL FOUR SIGNALS DOES THE
ENCRYPTED mRNA TURN ON AND SIX
COLUMNS, I BELIEVE.
LOOKS LIKE SIX COLUMNS.
IN EACH CASE I TREAT THE
RESPECTIVE CELL CULTURE WITH AN
ENCRYPTED mRNA AND BASICALLY
PROVIDE ONE OF FOUR OR ALL FOUR
SIGNALS BUT ONLY WHEN I PROVIDE
THE SIGNALS DOES THE mRNA TURN
ON AND UP TO THREE LOGS ABOVE
BACKGROUND SO HIGHLY RESPONSIVE
AND NOW IT'S SPECIFIC BECAUSE
IT'S AN AND GATE AND ONE THING
TO HINT YOU TOWARD THE FUTURE WE
CAN ACTIVATE THE ENCRYPTED RNA
AND TEST THE EFFICACY AGAINST
THE TUMOR.
THIS THE B16F10 MODEL FOR MICE.
A BLACK 6 MICE.
IF YOU WANT TO GIVE THEM A
TUMOR, SOUNDS TERRIBLE BUT WHAT
YOU TAKE MOUSE CANCER CELLS AND
IMPLANT THEM INTO MOUSE AND WAIT
A CERTAIN AMOUNT OF DAYS AND 10
DAYS AND SUBSEQUENTLY TREAT THEM
WITH A SHAM OR THE ACTIVATED
ENCRYPTED GMP RNA AND LOOK AT
TUMOR VOLUME AT THE GROWTH OF
THE CANCER AND OF YOU SEE THE
STATISTICALLY SIGNIFICANT KNOCK
DOWN IN TUMOR SIZE OR TUMOR
GROWTH.
SEE THE EFFICACY HERE.
I'LL END WITH THAT BECAUSE WE'RE
COMING TOWARD THE END OF THE
TALK AND I'VE GIVEN A PICTURE
HOW TO USE ENCRYPTED mRNA IN
VIRAL AND NON-VIRAL CONTEXT AND
HOW TO BUILD CANDIDATES
RESPONSIVE TO AN ARRAY OF
VIRUSES IN COMBINATION ENCRYPTED
mRNA'S ONE WE CALL AT225 AND
GOING BACK TO THE NATIONAL POINT
OF THE TALK MORE THAN DEVELOPING
THE CANDIDATES I'D SAY THE HIGH
LEVEL GOAL OF THE COMPANY IS TO
USE RNA IN SYNTHETIC BIOLOGY TO
CONTROL THE THERAPEUTIC WINDOW
OF NOVEL BIOLOGICS BY
CONTROLLING THE CAPACITY OF THE
PROTEINS THOSE RNAs ENCODE USING
RNA TO BUILD AUTONOMOUS
MEDICINES.
THANKS.
>> THANK YOU FOR THE TALK.
IT WAS VERY INTERESTING AND GOOD
STUFF.
ONE QUESTION I HAD ABOUT THE
VIRAL ENCODING RNAs.
I NEOTICED YOU HAD IT WIN THE
THERAPEUTIC PROTEIN OR WITH THE
OPPOSITE VIRUS.
WHAT ABOUT A CONSITUATIVE
PROT
PROTEIN?
>> EXCELLENT QUESTION.
WE'RE RIGHT.
WE HAD ALL THE COLUMNS AND I
PICKED THE RANDOM COLUMN AND
SAID THE HEIGHT REFLECT THE
KNOCK DOWN FROM THE mRNA.
YOU'RE RIGHT, IF YOU
CONSTITUATIVE CONTROL AND IF I
WERE TO ANSWER YOUR QUESTION IF
YOU'RE ASKING WHAT THE ADVANTAGE
WOULD BE WHAT I JUST IMPLIED.
YOU COULD HAVE SAFETY AND HAVE
PROPHYLACTIVE DELIVERY AND AVOID
WHERE A VIRUS ISN'T PRESENT.
DOES THAT ANSWER YOUR QUESTION?
>> I WAS WONDERING ABOUT THE
CONSTITUTIVE VIRUS.
>> THANK YOU FOR THE TALK.
I HAVE A QUESTION ABOUT THE KEY
TO YOUR LOCK.
COULD IT BE A LIPID MOLECULE AS
WELL?
I CAN THINK OF A MISSING ENZYME
WITH THE ACCUMULATION OF A LIPID
NORMALLY FOUND BUT REACHES TOXIC
LEVELS.
COULD THEY BE USED TO ACTIVATE
THE mRNA BUT IN A TARGETED WAY
LIKE SOME LIPIDS ARE ONLY
ACCUMULATING IN OLIGO
DENDROCYTES OR CERTAIN TISSUES.
I CAN THINK OF A WAY WE'D BE
ABLE TO DO THAT.
>> THE FIRST QUESTION IS
SOMETHING THAT MAYBE WAS NOT
MENTIONED IN TERMS OF IT BEING
PROPRIETARY.
I WAS WONDERING IF YOU CAN GIVE
A GENERAL OVERVIEW AS TO HINTS
OF WHAT THE MECHANISM OF THE
LOCKS IS BECAUSE I'M ENVISIONING
SOMETHING ALONG THE LINES OF
ACTOMERS OR RNAs THAT UNFOLD AND
GET UNLOCKED WHEN THEY'RE
EXPOSED TO SOMETHING ELSE.
I'D BE CURIOUS TOE ANYTHING YOU
SAY ABOUT THAT AND MY SECOND
QUESTION IS REGARDING VIRAL
VECTORS AND OTHER GENE DELIVERY
MECHANISMS BESIDES LIPOSOMES.
I'M WONDERING IF YOU EXPLORED
INVESTIGATIONS INTO COUPLING THE
RNA LOCKS WITH OTHER VECTORS
BESIDES MECHANISMS AND IF
THERE'S ADDITIONAL BENEFITS YOU
CAN ENVISION FOR THAT?
>> TO YOUR FIRST QUESTION, YES,
WE HAVE BEEN OPAQUE ABOUT THE
MECHANISM ACTION AND NEED TO BE
OPAQUE A LITTLE BIT LONGER AND
SEE HOW THEY WORK.
APOLOGIZE FOR NOT BEING MORE
FORTHRIGHT.
SECOND QUESTION, THE KEY THING
IS ACTUALLY THE RNA ITSELF.
YOU HAVE ANOTHER WAY TO
INTRODUCE INTO THE CELL WHETHER
A VIRAL OR PLASMID OR ANOTHER
WAY OF PRODUCING mRNA IS
AMENABLE TO HAVING THE WORK.
>> THANK YOU VERY MUCH.
REALLY ENGAGING TALK.
AND THERAPEUTICS ARE REQUIRED TO
BE DELIVERED A THOUSAND FOLD
HIGHER THAN mRNA VACCINES.
I DID NOT SEE ANY INDICATION IN
THE PRESENTATION THAT FOLLOWED
WHICH REFLECT A DECREASE IN THE
DOSAGE THAT WOULD IMPLY A
DECREASE SO IF YOU CAN SHED
LIGHT ON THAT.
>> THAT'S A FAIR POINT.
WE'RE STILL WORKING ON THE RANGE
WHERE ESPECIALLY FOR INFECTIOUS
DISEASE AND THE DOSES WE'RE
GIVING ARE ON THE ORDER OF WHAT
YOU WOULD NEED TO GENERATE AN
IMMUNE RESPONSE SO WE'RE GIVING
THE EQUIVALENT OF SOMETHING LIKE
A FEW HUNDRED MICROGRAMS PER
DOSE.
ESPECIALLY BECAUSE WE'RE GOING
TO A LOCAL AREA WE DON'T NEED
QUITE AS MUCH AS THE SYSTEMIC
TREATMENTS WHERE I NEED TO
PROVIDE ENOUGH TREATMENT FOR THE
WHOLE CIRCULATION.
>> IF I UNDERSTAND CORRECTLY YOU
HAVEN'T REALLY SOLVED THAT
PROBLEM.
YOU'RE JUST TARGETING YOUR
THERAPEUTICS TO A LOCALIZED
AREA?
>> I DON'T KNOW IF -- WELL, PART
OF THE LUTION IS PART IS --
>> YOU COULD DO THAT WITH
REGULAR RNA THERAPEUTICS?
>> THAT'S ONE POSSIBILITY.
WE CAN AMPLIFY THE DOSE AND WE
HAVE AN APPLICATION.
>> THANK YOU.
>> WE GET QUITE A BIT OF PROTEIN
FROM THE CONTEXT OF A TARGET.
THANKS.
>> THANK YOU VERY MUCH.
VERY ENGAGING DISCUSSION.
THANK YOU EVERYONE STICK AROUND
FOR THE SESSION AND THANK ALL
THREE SPEAKERS FOR THEIR
WONDERFUL PRESENTATIONS.
NOW IT'S TIME TO GO TO THE
POSTER SESSIONS.
ENJOY.