Reprogramming Human T Cell Circuitry

Genetic variation in T cells affects autoimmune diseases, infectious diseases and cancer immunotherapies. Our overall research goal is to identify genetic circuits that control human immune cell functions and understand how sequence variation throughout the genome can contribute to immune-mediated diseases. We have developed a CRISPR-Cas9 ribonucleoprotein (RNP) platform for genome editing in primary human T cells, which allows us to advance from genome mapping to genome perturbations. For the first time, we can readily re-write specific sequences in human T cells and interrogate the biological effects. Moreover, genome editing in primary human immune cells provides enormous opportunities to enhance the next generation of immunotherapies.