PMID: 9177238Jun 10, 1997Paper

Safety-modified episomal vectors for human gene therapy

Proceedings of the National Academy of Sciences of the United States of America
M J CooperJ Tan

Abstract

The effectiveness of ongoing gene therapy trials may be limited by the expression characteristics of viral and plasmid-based vectors. To enhance levels of heterologous gene expression, we have developed a safety-modified episomal expression vector that replicates extrachromosomally in human cells. This vector system employs a simian virus 40 (SV40) large T antigen mutant (107/402-T) that is deficient in binding to human tumor suppressor gene products, including p53, retinoblastoma, and p107, yet retains replication competence. These SV40-based episomes replicate to thousands of copies by 2-4 days after gene transfer in multiple types of human cell lines, with lower activity in hamster cells, and no detectable activity in dog, rat, and murine cell lines. Importantly, 107/402-T has enhanced replication activity compared with wild-type T antigen; this finding may be due, in part, to the inability of p53 and retinoblastoma to inactivate 107/402-T function. We demonstrate that the level and duration of 107/402-T expression regulates the observed episomal copy number per cell. Compared with standard plasmid constructs, episomes encoding 107/402-T yield approximately 10- to 100-fold enhanced levels of gene expression in unselected pop...Continue Reading

References

Jan 1, 1992·Current Topics in Microbiology and Immunology·J B Wilson, A J Levine
Jun 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J R BischoffD Beach
Dec 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·P N FriedmanC Prives
Apr 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·J M HorowitzR A Weinberg
Nov 1, 1990·Nature·B MossT R Fuerst
Jan 1, 1989·Journal of Virology·G LoeberP Tegtmeyer
Oct 1, 1987·Nature·A W BraithwaiteJ R Jenkins
Aug 12, 1985·Nucleic Acids Research·G BiamontiA Falaschi
Apr 1, 1973·Virology·F L Graham, A J van der Eb
Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·H HermekingD Eick
Apr 1, 1994·Molecular and Cellular Biology·S B HaaseM P Calos
Nov 1, 1993·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·A PuisieuxM Ozturk
Oct 1, 1993·Human Gene Therapy·M J Cooper, S Miron

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Citations

May 23, 2006·Pharmaceutical Research·Ethlinn V B van GaalEnrico Mastrobattista
Feb 17, 2000·Trends in Biotechnology·A Mountain
Mar 12, 2005·Nature Reviews. Genetics·Dominic J GloverDavid A Jans
Feb 7, 2008·Molecular Therapy : the Journal of the American Society of Gene Therapy·Rahul JandialEvan Y Snyder
Sep 6, 2000·European Journal of Biochemistry·K Van CraenenbroeckG Haegeman
Mar 28, 2008·Journal of Virology·Christopher B BuckBenes L Trus
Jul 1, 2004·Molecular and Cellular Biology·David M BarrettGordon D Ginder
Jul 8, 2010·Biological & Pharmaceutical Bulletin·Mana ItoHiroyuki Kamiya
Oct 7, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Rahel ZulligerMuna I Naash
Mar 3, 2009·Journal of Molecular Biology·Aristeidis GiannakopoulosAglaia Athanassiadou
Jan 30, 2008·Current Protocols in Cell Biology·Christopher B Buck, Cynthia D Thompson
Dec 10, 1999·Nature Biotechnology·K M GaenslerR J Debs
Jun 8, 2002·Molecular and Cellular Biology·Anthony W I LoJohn P Murnane
May 1, 2010·Biomolecular Concepts·Claudia HagedornSina Rupprecht
May 18, 1999·The American Journal of Physiology·R ChenJ R Raymond
Jul 19, 2012·Chemical Research in Toxicology·Hiroyuki Kamiya, Masahiro Kurokawa

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