DNA-damaging agents greatly increase the transduction of nondividing cells by adeno-associated virus vectors.
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.
Alexander
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IE
Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Russell
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DW
Miller
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AD
D000469:Alkaline Phosphatase / Q000032:analysis / Q000096:biosynthesis; D002460:Cell Line; D002478:Cells, Cultured; D002586:Cesium; D002945:Cisplatin / Q000494:pharmacology*; D004249:DNA Damage; D000229:Dependovirus / Q000187:drug effects / Q000235:genetics*; D005720:Gamma Rays; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D005822:Genetic Vectors / Q000187:drug effects / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D007231:Infant, Newborn; D007700:Kinetics; D008297:Male; D008727:Methotrexate / Q000494:pharmacology*; D015739:Nocodazole / Q000494:pharmacology; D012867:Skin; D014161:Transduction, Genetic / Q000187:drug effects / Q000528:radiation effects; D001616:beta-Galactosidase / Q000032:analysis / Q000096:biosynthesis
D002586:Cesium; D000469:Alkaline Phosphatase; D001616:beta-Galactosidase; D002945:Cisplatin; D015739:Nocodazole; D008727:Methotrexate