Fig. 2

Different methods for the generation of CAR T cells with site-specific CAR transgene integration. Defined locations are targeted in the T cell genome that are considered safe and efficient harbors for CAR transgene integration using different methods as follows: 1: Adeno-associated vectors mediate the delivery of CAR DNAs into T cells as well as their integration into the AAV1 loci on chromosome 19 through binding their receptors on the surface of T cells. 2: Recombinant Adeno-associated viruses (rAAV) accompanied by engineered homing nucleases can edit the T cell genome at sites that are specified by engineering a homing nuclease that transports and places a CAR construct precisely at the desired location. 3, 4, and 5: The latest genome-editing technologies that can be used to insert CAR transgenes into desired target locations in the T cell genome