Project Grant R43HG013446

A UNIQUELY SCALABLE APPROACH TO SINGLE CELL SEQUENCING FOR THE DEVELOPMENT OF NEXT GENERATION CELL THERAPIES - IMMUNOTHERAPIES (INCLUDING CAR-T CELL THERAPIES) ARE WONDER DRUGS WHEN THEY WORK, BUT THE RESPONSE RATES OF TODAY'S IMMUNOTHERAPIES ARE ONLY 15-20% AND THERAPY COSTS REMAIN PROHIBITIVELY HIGH FOR MASS ADOPTION. SINGLE-CELL SEQUENCING (SC-SEQ) IS BECOMING THE PREFERRED TOOL FOR IMMUNE PROFILING TO MAP A PATIENT'S ADAPTIVE IMMUNE RESPONSE, AND TO READOUT PHENOTYPIC CHANGES THAT RESULT FROM CRISPR BASED GENE EDITS AT THE SINGLE CELL LEVEL. HOWEVER, THE FULL POTENTIAL OF SC-SEQ BASED CRISPR SCREENS AND IMMUNE REPERTOIRE PROFILING FOR THE DEVELOPMENT OF NEXT GENERATION THERAPEUTICS REQUIRES A 10-FOLD TO 100-FOLD INCREASE IN CELL THROUGHPUT RELATIVE TO CURRENT PLATFORMS. UPCOMING EXPIRATION OF ILLUMINA'S CORE IP RE-IGNITED COMPETITION IN US & EU MARKETS. THE RESULTING RE-ACCELERATION IN THE DROP OF DNA SEQUENCING COSTS (6-FOLD PRICE REDUCTION IN 2023 VS. ILLUMINA'S 2022 PRICING) MAKES SC-SEQ OF 10 MILLION CELLS AFFORDABLE TODAY (20-30 MILLION CELLS IN ~3 YEARS AND 100 MILLION CELLS IN 6 YEARS), BUT EXISTING METHODS FOR SC-SEQ DO NOT SUPPORT THROUGHPUT BEYOND 1 MILLION CELLS PER EXPERIMENT. PROPOSED ALTERNATIVES ARE SCALABLE, BUT TRADE-OFFS IN PERFORMANCE AND EASE-OF-USE MAKE THEM UNSUITABLE FOR TRANSLATIONAL RESEARCH. SANSIMEON'S APPROACH UNIQUELY SCALES SC-SEQ WITH THROUGHPUT >100M CELLS, WHILE RETAINING THE EASE-OF-USE AND NECESSARY CELL CAPTURE EFFICIENCY FOR HIGH-THROUGHPUT APPLICATIONS IN TRANSLATIONAL RESEARCH. OUR PLATFORM INCORPORATES A TECHNOLOGY FOR IN-LINE SAMPLE DEBULKING, WHICH WAS PREVIOUSLY COMMERCIALIZED FOR APPLICATIONS IN CELL THERAPY MANUFACTURING AND RARE CELL ISOLATION. SANSIMEON'S ABILITY TO SEQUENCE >100 MILLION SINGLE CELLS DIRECTLY FROM CRUDE & COMPLEX SAMPLES (SUCH AS WHOLE BLOOD OR BONE MARROW ASPIRATES), WITH A SINGLE-STEP AUTOMATED WORKFLOW, MAKES THE PLATFORM IDEALLY SUITED FOR HIGH-THROUGHPUT APPLICATIONS IN TRANSLATIONAL RESEARCH.