Abstract: Provided herein are genome-edited ?? T cells that exhibit an increased capacity to kill cancer cells, methods of producing genome-edited ?? T cells, and methods of treating or preventing a condition by administering genome-edited ?? T cells to a subject in need thereof.

Abstract: Provided herein are methods and systems for targeted gene disruption (knock-out, missense mutation) and targeted gene knock-in in mammalian cells using base editors and guide RNAs (gRNAs) designed to target splice acceptor-splice donor sites. Also provided herein are universally acceptable genetically engineered cells comprising targeted disruptions in immunotherapy-related genes and comprising a CAR/TCR for therapeutic applications.