Adenoviral vectors with reduced TNF response and partial E3 region deletion

摘要

Adenoviral vectors with a deletion of the E3 region such that the remaining E3 region reduces the TNF response of a host mammalian cell infected with the virus. The portion of the E3 region remaining in these vectors encodes the 14.7 kD protein, and may also contain a deletion of at least the E1a promoter. These partially deleted E3 vectors will inhibit the host cell's immune response so that the infected cell will live longer. Any non-adenoviral gene expressed from these vectors in the infected cell will be produced for a longer length of time and achieve a higher concentration than when adenoviral vectors not expressing function 14.7 kD protein are used. These 14.7 kD expressing adenoviral vectors will be useful for gene therapy and especially in cancer gene therapy where the non-adenoviral DNA sequence being expressed are preferably cytokine genes, such as IL-1, and suicide genes, such as HSV-tk. The vectors also are useful for antisense therapy.