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Precision genome engineering with programmable DNA-nicking enzymes

Cited 96 time in Web of Science Cited 103 time in Scopus
Authors
Kim, Eunji; Kim, Sojung; Kim, Duk Hyoung; Choi, Beom-Soon; Choi, Ik-Young; Kim, Jin-Soo
Issue Date
2012-07
Citation
Genome Research, Vol.22 No.7, pp.1327-1333
Abstract
Zinc finger nucleases (ZFNs) are powerful tools of genome engineering but are limited by their inevitable reliance on error-prone nonhomologous end-joining (NHEJ) repair of DNA double-strand breaks (DSBs), which gives rise to randomly generated, unwanted small insertions or deletions (indels) at both on-target and off-target sites. Here, we present programmable DNA-nicking enzymes (nickases) that produce single-strand breaks (SSBs) or nicks, instead of DSBs, which are repaired by error-free homologous recombination (HR) rather than mutagenic NHEJ. Unlike their corresponding nucleases, zinc finger nickases allow site-specific genome modifications only at the on-target site, without the induction of unwanted indels. We propose that programmable nickases will be of broad utility in research, medicine, and biotechnology, enabling precision genome engineering in any cell or organism.
ISSN
1088-9051
URI
http://hdl.handle.net/10371/165623
DOI
https://doi.org/10.1101/gr.138792.112
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