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Zinc fingers hit off target

Nature Medicine volume 17, pages 1192–1193 (2011)Cite this article

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There has been a lot of excitement about the potential applications of zinc finger nucleases (ZFNs), as these enzymes allow highly specific, targeted genome modification in live cells. ZFN-mediated gene correction is more specific than the viral integration methods currently used in gene therapy, and two ZFNs are currently in clinical trials for treating HIV and cancer. However, two new papers by Pattanayak et al.1 and Gabriel et al.2 raise questions about the purported specificity of these genome modification tools. They show that ZFNs, in addition to cleaving at their desired sites, can also have unexpected cleavage effects in vivo that cannot be predicted using conventional in silico analyses. These findings could have important consequences for the safe use and optimization of ZFNs in gene therapy. We asked four experts to comment on the implications of this study.

Linzhao Cheng

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References

  1. Pattanayak, V., Ramirez, C.L., Joung, J.K. & Liu, D.R. Revealing off-target cleavage specificities of zinc-finger nucleases by in vitro selection. Nat. Meth. 8, 765–770 (2011).

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Competing interests

K.H. is a co-inventor on a pending patent using zinc finger nucleases to do genome editing in hemophilia.

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Zinc fingers hit off target. Nat Med 17, 1192–1193 (2011). https://doi.org/10.1038/nm1011-1192

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