Human gene targeting by viral vectors

被引:232
作者
Russell, DW [1 ]
Hirata, RK
机构
[1] Univ Washington, Sch Med, Markey Mol Med Ctr, Seattle, WA 98195 USA
[2] Univ Washington, Sch Med, Dept Med, Div Hematol, Seattle, WA 98195 USA
关键词
D O I
10.1038/ng0498-325
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Stable transduction of mammalian cells typically involves random integration of viral vectors by non-homologous recombination. Here we report that Vectors based on adeno-associated virus (AAV) can efficiently modify homologous human chromosomal target sequences. Bath integrated neomycin phosphotransferase genes and the hypoxanthine phosphoribosyltransferase gene were targeted by AAV vectors. Site-specific genetic modifications could be introduced into approximately 1% of cells, with the highest targeting rates occurring in normal human fibroblasts. These results suggest that AAV vectors could be used to introduce specific genetic changes into the genomic DNA of a wide variety of mammalian cells. including therapeutic gene targeting applications.
引用
收藏
页码:325 / 330
页数:6
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