Project Grant R44GM140750

HIDEF B8: COMMERCIALIZATION AND SCALED PRODUCTION OF DEFINED, ROBUST, AND COST-EFFECTIVE MEDIA FOR IPSCS - RESEARCH & RELATED OTHER PROJECT INFORMATION DEFINED BIOSCIENCE, INC. 7. PROJECT SUMMARY INCONSISTENCY OF GROWTH MEDIA FOR CELL CULTURE IS A SIGNIFICANT PROBLEM IN BOTH INDUSTRY AND ACADEMIA THAT HAS PLAGUED LABORATORIES FOR DECADES. IN BIOPHARMA, CELL-BASED AND CELL-DERIVED THERAPIES ARE GROWING AT A TREMENDOUS RATE AND REQUIRE WELL-DEFINED, ANIMAL-FREE COMPONENTS TO MEET FDA AND CGMP REGULATIONS. IT IS THEREFORE NOT SURPRISING THAT THERE IS AN INCREASED NEED FOR AND ADOPTION OF SERUM-FREE MEDIA FOR CELL CULTURE GROWTH THAT IS ATTRIBUTED TO ITS SUPERIOR BATCH-TO-BATCH CONSISTENCY AND REDUCED RISK OF UNWANTED ANIMAL/XENOBIOTIC CONTAMINANTS. THIS IS PARTICULARLY CRITICAL TO HUMAN INDUCED PLURIPOTENT STEM CELLS (HIPSCS), A RAPIDLY EVOLVING TECHNOLOGY WITH WIDE RESEARCH AND CLINICAL APPLICATION. THESE CELLS PRESENT NUMEROUS ADVANTAGES COMPARED TO PREVIOUS TECHNOLOGIES, INCLUDING HUMAN ORIGIN, THE ABILITY TO FORM MULTI-CLASS CELL SYSTEMS AND TISSUES, RELATIVE EASE OF PRODUCTION AND MODIFICATION, AND FUNCTIONAL RELEVANCE. ROBUST AND WELL- CHARACTERIZED PROTOCOLS ARE OF UTMOST IMPORTANCE WHEN CULTURING HIPSCS FOR DOWNSTREAM APPLICATIONS. HIGH PLURIPOTENCY, GENETIC STABILITY, LARGE-SCALE PRODUCTION AND MAINTAINED FUNCTION ALL MUST BE KEPT IN MIND FOR HIPSCS. YET DESPITE THE ARRAY OF DEFINED MEDIA NOW AVAILABLE FOR IPSCS, MANY OF THESE MEDIA FAIL TO SATISFY THE FULL NEEDS OF HIPSC RESEARCH, INCLUDING ROBUSTNESS OVER MULTIPLE PASSAGES AND EXPERIMENTAL NEEDS, LOW COST, EASE OF PRODUCTION, WEEKEND-FREE MEDIA CHANGES AND FULLY DEFINED COMPONENTS. SUCH TRAITS ARE CRITICAL FOR ROBUST, CONSISTENT AND AFFORDABLE RESEARCH IN THE HIPSC SPACE. JUST THIS YEAR, OUR DEFINED BIOSCIENCE TEAM EMPIRICALLY TESTED COMMON DEFINED MEDIA COMPONENTS OVER A LARGE ARRAY OF CONCENTRATIONS AND COMBINATIONS, ISOLATING A WELL-DEFINED RECIPE WITH HIGH ROBUSTNESS, EFFICACY OVER >100 CELL PASSAGES, AND MAINTAINED SUCCESS IN A WEEKEND-FREE PASSAGING SCHEDULE. THIS MEDIA, TERMED B8 BY THE LAB OF SCIENTIFIC ADVISORY BOARD MEMBER PAUL BURRIDGE, MET OR EXCEEDED THE EXPECTATIONS FOR A PHASE I SBIR DEVELOPMENT PROPOSAL. HERE WE WILL EXTEND THIS WORK TO PREPARE HIDEF B8, A FORMULATION OF B8 FINALIZED TO OPTIMAL COMPONENT CONCENTRATIONS AND REDUCED COST. THIS OPTIMIZED FORMULATION WILL BE TESTED ACROSS ACADEMIC AND INDUSTRIAL LABS IN THE UNITED STATES TO CONFIRM ROBUSTNESS AND EFFICACY IN STREAMLINED AND APPLIED HIPSC CULTURE AND METHODOLOGIES. WE INTEND TO MAKE HIDEF B8 AN AFFORDABLE, DEFINED MEDIA FOR ROBUST HIPSC CULTURE ACROSS HIGH PASSAGE NUMBERS AND IN A WEEKEND-FREE CONTEXT, SIGNIFICANTLY REDUCING THE COST AND COMPLEXITY OF HIPSC TECHNOLOGIES ACROSS THE FIELD. THIS WILL ENABLE STABLE CELL CULTURE AND A WELL-CHARACTERIZED STARTING POINT FOR SUBSEQUENT DIFFERENTIATION AND APPLIED HIPSC TECHNOLOGY EFFORTS, WHILE SIMULTANEOUSLY LOWERING THE BARRIER OF ENTRY FOR HIPSC DEVELOPMENT IN THE FIELD.