Oncolytic Vaccinia Virus

A TK-deficient vaccinia virus comprising an inactivated N1L gene, wherein the N1L gene is inactivated by the insertion of a single expression cassette, said expression cassette comprising a nucleic acid sequence, said nucleic acid sequence encoding a single heterologous polypeptide, and wherein the nucleic acid sequence comprises at least three vaccinia virus promoters positioned in the same orientation, wherein the orientation of the vaccinia virus promoters is opposite to that of the adjacent intact reading frame L024.

A composition comprising a TK-deficient vaccinia virus, wherein the virus comprises an inactivated N1L gene, wherein the N1L gene is inactivated by the insertion of a single expression cassette, said expression cassette comprising a nucleic acid sequence, said nucleic acid sequence encoding a single heterologous polypeptide, and wherein the nucleic acid sequence comprises at least three vaccinia virus promoters positioned in the same orientation, wherein the orientation of the vaccinia virus promoters is opposite to that of the adjacent intact reading frame L024, optionally in the presence of a pharmaceutically acceptable carrier or excipient.

A method of treating cancer, the method comprising administering to a subject a TK-deficient vaccinia virus, wherein the virus comprises an inactivated N1L gene, wherein the N1L gene is inactivated by the insertion of a single expression cassette, said expression cassette comprising a nucleic acid sequence, said nucleic acid sequence encoding a single heterologous polypeptide, and wherein the nucleic acid sequence comprises at least three vaccinia virus promoters positioned in the same orientation, wherein the orientation of the vaccinia virus promoters is opposite to that of the adjacent intact reading frame L024.