ADENOVIRAL PRETERMINAL PROTEIN STABILIZES MINI-ADENOVIRAL GENOMES IN-VITRO AND IN-VIVO

In the absence of host immunity, nonintegrating, first-generation aden oviral vectors remain stable in the nucleus of quiescent transduced ce lls in mice. A mini-adenoviral genome (9 kb) deleted for viral El, E2, E3, and late genes, but containing the viral inverted terminal repeat s (ITRs), transgene expression cassette (human alpha(1)-antitrypsin), and the viral E4 genes was equally efficient at transducing cells in v itro or in vivo as first generation, E1-deleted vectors. In contrast t o a first generation vector, gene expression as well as vector DNA was short-lived in cells transduced with the deleted adenoviral genome. W e demonstrate that coexpression of the adenoviral E2-preterminal prote in from the vector or in trans stabilizes the mini-genome in vitro and in vivo without evidence of cellular toxicity.