Extended Data Fig. 1

Scheme of genome editing of PDL1 by eOA effectively improved virotherapy and adoptive T-cell therapy. First, eOA encoding Cas9 editor and sgRNA targeting PDL1 was engineered, and eOA was further shielded by an engineered biological membrane presenting T cell-specific antigens in two ways to form M@eOA. Finally, M@eOA was physically attached onto carrier T cell surfaces by recognizing TCR or CAR through antigen-receptor interaction to form ONCOTECH. By virtue of tumor-targeting ability of T cells, ONCOTECH could reach tumor following the systemic administration, and eOAs were readily released once carrier T cells reach the surface of tumor cells and recognize their cognate tumor-specific antigens through competitive antigen-receptor interaction and membrane fusion. The OAs were then internalized by cancer cells and facilitate specific viral infection. After infection, oncolytic virus constructs encoding Cas9 editor could disrupt PDL1 gene of tumor cells to downregulate their PD-L1 expression, which greatly contributes to mitigating the immunosuppressive TME and promoting both T-cell therapy and oncolysis against tumors.