The ability to achieve site-specific manipulation of the mammalian genome has 
widespread implications for basic and applied research. Gene targeting is a 
process in which a DNA molecule introduced into a cell replaces the 
corresponding chromosomal segment by homologous recombination, and thus presents 
a precise way to manipulate the genome. In the past, the application of gene 
targeting to mammalian cells has been limited by its low efficiency. Zinc finger 
nucleases (ZFNs) show promise in improving the efficiency of gene targeting by 
introducing DNA double-strand breaks in target genes, which then stimulate the 
cell's endogenous homologous recombination machinery. Recent results have shown 
that ZFNs can be used to create targeting frequencies of up to 20% in a human 
disease-causing gene. Future work will be needed to translate these in vitro 
findings to in vivo applications and to determine whether zinc finger nucleases 
create undesired genomic instability.