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 alpha(1)-antitryp sin (hAAT) or canine factor IX (cFIX) were modified so that they also contained a temperature-sensitive mutation (ts125) in the DNA binding protein encoded within the viral E2A region. The effects of the inclus ion of the ts125 mutation on transgene expression in vivo were evaluat ed in Balb/c mice and hemophilia B dogs by comparison with adenoviral vectors containing the same transgene but lacking the ts125 mutation. No significant differences in the duration of transgene expression wer e observed in either animal model. Insufficiency of the ts125 mutation in the prolongation of transgene expression in these two animal model s suggests that further modification of the vector backbone may be req uired to achieve long-term gene expression in a wide variety of applic ations. Additionally, humoral immune response to transgene products ha s been demonstrated in immunocompetent animal models, which will also need to be surmounted for long-term efficacy in disease treatment by g ene therapy.