Adeno-associated virus vectors preferentially transduce cells in S phase.
Vectors based on adeno-associated virus can stably transfer genes by chromosomal integration in recipient cells. In this study we have infected stationary and dividing primary human fibroblast cultures with adeno-associated virus vectors encoding alkaline phosphatase and neomycin phosphotransferase. We find that the transduction frequency of S phase cells is about 200 times that of non-S phase cells. However, neither S phase nor mitosis is essential for transduction. Single-stranded vector genomes survive in stationary cultures and can be recruited for transduction by stimulating these cultures to divide. Stable transductants contain randomly integrated vector sequences. These findings have important implications for the use of adeno-associated virus vectors in gene therapy.
Russell
D W
DW
Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Miller
A D
AD
Alexander
I E
IE
D000469:Alkaline Phosphatase; D002478:Cells, Cultured; D000229:Dependovirus / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D066298:In Vitro Techniques; D010957:Plasmids; D016196:S Phase; D014161:Transduction, Genetic; D016662:Virus Integration
D000469:Alkaline Phosphatase