Lack of persistence of E1^- recombinant adenoviral vectors containing a temperature-sensitive E2A mutation in immunocompetent mice and hemophilia B dogs

Two recombinant adenoviruses expressing either human α₁-antitrypsin (hAAT) or canine factor IX (cFIX) were modified so that thy also contained a temperature-sensitive mutation (ts 125) in the DNA binding protein encoded within the viral E2A region. The effects of the inclusion of the ts 125 mutation on transgene expression in vivo were evaluated in Balb/c mice and hemophilia B dogs by comparison with adenoviral vectors containing the same transgene but lacking the ts 125 mutation. No significant difference in the duration of transgene expression were observed in either animal model. Insufficiency of the ts 125 mutation in the prolongation of transgene expression in these two animal models suggests that further modification of the vector backbone may be required to achieve long-term gene expression in a wide variety of applications. Additionally, humoral immune response to transgene products has been demonstrated in immunocompetent animal models, which also need to be surmounted for long-term efficacy in disease treatment by gene therapy.