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PMID: 7966621 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

DNA-damaging agents greatly increase the transduction of nondividing cells by adeno-associated virus vectors.

Journal of virology ·Vol. 68 ·No. 12 ·1994-12-00 ·Pages 8282-7

Alexander IE, Russell DW, Miller AD

Abstract

None of the vector systems currently available for gene therapy applications have been shown to be capable of both efficient gene transfer into nondividing cells and long-term expression through stable integration into host cell DNA. While integrating vectors based on adeno-associated virus are capable of mediating gene transfer into nondividing cells, this process is 200-fold less efficient than transduction of dividing cells. We demonstrate that the transduction efficiency of adeno-associated virus vectors can be increased by treatment with DNA-damaging agents. Nondividing cells are especially responsive, with increases in transduction efficiency of up to 750-fold. This finding has the potential to facilitate gene therapy applications requiring gene transfer to nondividing cells.

MeSH Terms
Alkaline Phosphatase/analysis,biosynthesis Cell Line Cells, Cultured Cesium Cisplatin/pharmacology DNA Damage Dependovirus/drug effects,genetics Gamma Rays Gene Expression/drug effects,radiation effects Genetic Vectors/drug effects,radiation effects HeLa Cells Humans Infant, Newborn Kinetics Male Methotrexate/pharmacology Nocodazole/pharmacology Skin Transduction, Genetic/drug effects,radiation effects beta-Galactosidase/analysis,biosynthesis
Chemicals
Cesium Alkaline Phosphatase beta-Galactosidase Cisplatin Nocodazole Methotrexate
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Alexander I E
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Russell D W
Miller A D
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29 references, click to expand
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.68.12.8282-8287.1994
Published
1994-12-00
Pages
8282-7
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC237296
Subset
IM
Grants
NCI NIH HHS · CA09645 · United States
NIDDK NIH HHS · DK47754 · United States
NHLBI NIH HHS · HL41212 · United States
External Links
PubMed source DOI: 10.1128/JVI.68.12.8282-8287.1994 PMC Full Text View journal details
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