PMID: 8971024Dec 1, 1996Paper

Recombinant adenoviruses with large deletions generated by Cre-mediated excision exhibit different biological properties compared with first-generation vectors in vitro and in vivo

Journal of Virology
A LieberM A Kay

Abstract

In vivo gene transfer of recombinant E1-deficient adenoviruses results in early and late viral gene expression that elicits a host immune response, limiting the duration of transgene expression and the use of adenoviruses for gene therapy. The prokaryotic Cre-lox P recombination system was adapted to generate recombinant adenoviruses with extended deletions in the viral genome (referred to here as deleted viruses) in order to minimize expression of immunogenic and/or cytotoxic viral proteins. As an example, an adenovirus with a 25-kb deletion that lacked E1, E2, E3, and late gene expression with viral titers similar to those achieved with first-generation vectors and less than 0.5% contamination with E1-deficient virus was produced. Gene transfer was similar in HeLa cells, mouse hepatoma cells, and primary mouse hepatocytes in vitro and in vivo as determined by measuring reporter gene expression and DNA transfer. However, transgene expression and deleted viral DNA concentrations were not stable and declined to undetectable levels much more rapidly than those found for first-generation vectors. Intravenous administration of deleted vectors in mice resulted in no hepatocellular injury relative to that seen with first-generation v...Continue Reading

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Citations

Mar 5, 1998·Circulation Research·M B DeYoung, D A Dichek
Jan 29, 2000·Brain : a Journal of Neurology·J KamholzM E Shy
Sep 15, 2000·Human Gene Therapy·D S SteinwaerderA Lieber
Nov 11, 2019·FEBS Letters·Chang Li, André Lieber
Jul 8, 1998·Proceedings of the National Academy of Sciences of the United States of America·M A MorsyC T Caskey
Dec 5, 1997·Proceedings of the National Academy of Sciences of the United States of America·M A KayP M Hoogerbrugge
Oct 27, 1999·Proceedings of the National Academy of Sciences of the United States of America·N MorralA L Beaudet
Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·M A KayC B Wilson
Jan 19, 2002·Journal of Virology·Gudrun SchiednerStefan Kochanek
Feb 23, 2000·Journal of Virology·D M ShayakhmetovA Lieber
Feb 3, 2000·Proceedings of the National Academy of Sciences of the United States of America·V SandigC T Caskey
Jun 15, 2005·Annual Review of Biochemistry·Inder M Verma, Matthew D Weitzman

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