Russell D W, Hirata R K
Markey Molecular Medicine Center, Department of Medicine, University of Washington School of Medicine, Seattle 98195-7720, USA.
Nat Genet. 1998 Apr;18(4):325-30. doi: 10.1038/ng0498-325.
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. Both 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.
哺乳动物细胞的稳定转导通常涉及病毒载体通过非同源重组随机整合到基因组中。在此，我们报道基于腺相关病毒（AAV）的载体能够有效地修饰人类同源染色体靶序列。新霉素磷酸转移酶基因和次黄嘌呤磷酸核糖转移酶基因的整合均能被AAV载体靶向。位点特异性基因修饰可导入约1%的细胞中，在正常人成纤维细胞中靶向率最高。这些结果表明，AAV载体可用于将特定的基因改变引入多种哺乳动物细胞的基因组DNA中，包括治疗性基因靶向应用。
