Human T cells are critical effectors of immune protection from infections, autoimmune pathology, and cancer immunotherapy. We use CRISPR-mediated gene editing in primary human T cells to systematically identify genetic targets that modulate the functions of T cells in contexts ranging from immunosuppression to cancer killing. By developing and applying CRISPR based methodologies such as pooled knock-in screening, CRISPR activation, and CRISPR interference, we are pinpointing the regulatory networks controlling T cell phenotypes as well as synthetic genetic programs that can be engineered into T cells to improve their utility as cell-based therapies for disease. We are working towards a range of genetically engineered cell therapies for cancer, autoimmunity, infections and other diseases.
1. Discuss current approaches for CRISPR genome editing in primary human T cells
2. Review progress toward clinical genome editing with non-viral knockin strategies
3. Discuss application of genome-wide screens as discovery platform for enhanced cellular therapies