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Nat Genet. 1998 Apr;18(4):325-30.

Human gene targeting by viral vectors.

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1
Markey Molecular Medicine Center, Department of Medicine, University of Washington School of Medicine, Seattle 98195-7720, USA. drussell@u.washington.edu

Abstract

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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PMID:
9537413
PMCID:
PMC3010411
DOI:
10.1038/ng0498-325
[Indexed for MEDLINE]
Free PMC Article
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