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Staying on target with CRISPR-Cas

Nature Biotechnology volume 31, pages 807–809 (2013)Cite this article

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Four independent studies shed light on the specificity of RNA-guided genome editing tools based on the Streptococcus pyogenes Cas9 protein.

We are in the midst of a revolution in genome engineering. The advent of targetable nucleases has given researchers the ability to induce specific double-strand breaks in chromosomal DNA whose repair either induces local mutations or stimulates homologous recombination with experimenter-provided donor DNA1. Until now, zinc-finger nucleases (ZFNs)2 and the more recently described transcription activator-like effector nuclease (TALEN) system3 have provided impetus to the field. In the past 12 months, a new entrant—the CRISPR-Cas RNA-guided nucleases4—have gained prominence. Compared with ZFNs and TALENs, these latter endonucleases not only offer a simpler means of attaining specificity (i.e., a guide RNA, rather than a DNA-binding protein domain that requires complex engineering) but also demonstrate equal or greater cleavage efficacy. One key question concerning the specificity of CRISPR-Cas RNA-guided nucleases is whether off-target cleavage is comparable to other endonuclease systems. In this issue, four studies4,5,6,7 provide new insights into the targeting efficiency of the CRISPR-Cas system, suggesting that the current generation of RNA-guided nucleases may not yet have adequate specificity to completely displace their ZFN and TALEN forebears.

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Figure 1: The sgRNA:Cas9 targeting complex.

References

  1. Jasin, M. Trends Genet. 12, 224–228 (1996).

    Article  CAS  Google Scholar 

  2. Carroll, D. Genetics 188, 773–782 (2011).

    Article  CAS  Google Scholar 

  3. Joung, J.K. & Sander, J.D. Nat. Rev. Mol. Cell Biol. 14, 49–55 (2013).

    Article  CAS  Google Scholar 

  4. Fu, Y. et al. Nat. Biotechnol. 31, 822–826 (2013).

    Article  CAS  Google Scholar 

  5. Hsu, P.D. et al. Nat. Biotechnol. 31, 827–832 (2013).

    Article  CAS  Google Scholar 

  6. Mali, P. et al. Nat. Biotechnol. 31, 833–838 (2013).

    Article  CAS  Google Scholar 

  7. Pattanayak, V. et al. Nat. Biotechnol. 31, 839–843 (2013).

    Article  CAS  Google Scholar 

  8. Sorek, R., Lawrence, C.M. & Wiedenheft, B. Annu. Rev. Biochem. 82, 237–266 (2013).

    Article  CAS  Google Scholar 

  9. Cong, L. et al. Science 339, 819–823 (2013).

    Article  CAS  Google Scholar 

  10. Cho, S.W., Kim, S., Kim, J.M. & Kim, J.-S. Nat. Biotechnol. 31, 230–232 (2013).

    Article  CAS  Google Scholar 

  11. Jinek, M. et al. eLife 2, e00471 (2013).

    Article  Google Scholar 

  12. Mali, P. et al. Science 339, 823–826 (2013).

    Article  CAS  Google Scholar 

  13. Jiang, W., Bikard, D., Cox, D., Zhang, F. & Marraffini, L.A. Nat. Biotechnol. 31, 233–239 (2013).

    Article  CAS  Google Scholar 

  14. Wang, H. et al. Cell Reports 153, 910–918 (2013).

    CAS  Google Scholar 

  15. Li, D. et al. Nat. Biotechnol. 31, 681–683 (2013).

    Article  CAS  Google Scholar 

  16. Li, W., Teng, F., Li, T. & Zhou, Q. Nat. Biotechnol. 31, 684–686 (2013).

    Article  CAS  Google Scholar 

  17. Jao, L.-E., Wente, S.R. & Chen, W. Proc. Natl. Acad. Sci. USA (2013) Epub ahead of print doi:10.1073/pnas.1308335110.

    Article  CAS  Google Scholar 

  18. Li, J.F. et al. Nat. Biotechnol. 31, 688–691 (2013).

    Article  CAS  Google Scholar 

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  1. Dana Carroll is at the Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, Utah.,

    Dana Carroll

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Correspondence to Dana Carroll.

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Carroll, D. Staying on target with CRISPR-Cas. Nat Biotechnol 31, 807–809 (2013). https://doi.org/10.1038/nbt.2684

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