ADENOASSOCIATED VIRUS VECTORS PREFERENTIALLY TRANSDUCE CELLS IN S-PHASE

被引:248
作者
RUSSELL, DW
MILLER, AD
ALEXANDER, IE
机构
[1] FRED HUTCHINSON CANC RES CTR, SEATTLE, WA 98104 USA
[2] UNIV WASHINGTON, SCH MED, DIV HEMATOL, SEATTLE, WA 98195 USA
[3] UNIV WASHINGTON, SCH MED, DEPT PATHOL, SEATTLE, WA 98195 USA
关键词
GENE THERAPY; CELL CYCLE;
D O I
10.1073/pnas.91.19.8915
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:8915 / 8919
页数:5
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