Nature Genetics
18, 325 - 330 (1998)
doi:10.1038/ng0498-325
Human gene targeting by viral vectorsDavid W. Russell1
& Roll K. Hirata1
1Markey Molecular Medicine Center and Division of Hematology, Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98195-7720, USA. e-mail: drussell@ii.washington.edu 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.
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