Adenoviral preterminal protein stabilizes mini-adenoviral genomes in vitro and in vivo.
In the absence of host immunity, nonintegrating, first-generation adenoviral vectors remain stable in the nucleus of quiescent transduced cells in mice. A mini-adenoviral genome (9 kb) deleted for viral E1, E2, E3, and late genes, but containing the viral inverted terminal repeats (ITRs), transgene expression cassette (human alpha 1-antitrypsin), and the viral E4 genes was equally efficient at transducing cells in vitro or in vivo as first generation, E1-deleted vectors. In contrast to a first generation vector, gene expression as well as vector DNA was short-lived in cells transduced with the deleted adenoviral genome. We demonstrate that coexpression of the adenoviral E2-preterminal protein from the vector or in trans stabilizes the mini-genome in vitro and in vivo without evidence of cellular toxicity.
Lieber
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Department of Medicine, University of Washington, Seattle 98195, USA.
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Kay
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D000256:Adenoviridae / Q000235:genetics*; D000410:Alanine Transaminase / Q000032:analysis; D000818:Animals; D002478:Cells, Cultured; D004279:DNA, Viral / Q000008:administration & dosage / Q000032:analysis / Q000633:toxicity; D005260:Female; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000235:genetics*; D005814:Genes, Viral / Q000235:genetics*; D005822:Genetic Vectors; D016679:Genome, Viral; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics*; D010957:Plasmids; D011498:Protein Precursors / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics*
D004279:DNA, Viral; D010750:Phosphoproteins; D011498:Protein Precursors; D014157:Transcription Factors; D014764:Viral Proteins; C085476:pTP protein, adenovirus; D000410:Alanine Transaminase