A non-viral gene editing platform for cell therapies and translational autoimmune disease modeling

SUMMARY Gene edited T lymphocytes hold promise as safe and effective living therapies for a wide range of human diseases, including autoimmune disease. However, viral methods currently employed to engineer cells for therapy are imprecise, exorbitantly expensive, and have high failure rates. These drawbacks limit development of cell therapies and prevent them from penetrating alternative markets, where natural, spontaneous disease can be addressed in pre-IND and IND-enabling studies to improve therapeutic outcomes. This proposal is focused on optimizing and advancing the development of a novel, non-viral method for highly efficient and precise engineering of human T cells. The innovation is a nanoplasmid-based, site-specific gene editing platform that enables tunable manufacturing of human cell therapeutics. Not only will this precise gene editing platform yield a quantum leap forward in cellular engineering, but the resultant product will also provide sustained clinical improvements over the standard of care for B cell–mediated autoimmune diseases, for which no current cell therapies exist. This Phase I proposal is focused on optimizing the efficiency of the GeneWeld site-specific gene editing platform and demonstrating the in vitro functionality of using GeneWeld to reprogram human Chimeric Antigen Receptor (CAR)-T cells for elimination of a targeted B cell population.