An AAV variant enables human T cell engineering in vivo

Engineering human T cells in vivo holds promise to conquer these limitations but requires effective T cell-targeted CAR delivery with demonstrated safety. Recombinant adeno-associated virus (rAAV) emerged as a promising vehicle in eight FDA-approved gene therapy drugs and shows attractive potential in tropism redirection via capsid engineering.

Here, we showcased that T-cell-tropic rAAV variants successfully enabled CAR expression in human T cells and de-targeted from the liver down to 1% of the parental serotypes. In a humanized mouse model, systematic injection of rAAV-CAR turned up to 8.3% of human T cells into CAR-T cells, which successfully eliminated the number of B cells and controlled tumor progression. Moreover, we identified and verified three cell surface receptors corresponding to the superior transduction efficiencies of the rAAV variants to T cells.