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Genome editing by natural and engineered CRISPR-associated nucleases

Nature Chemical Biologyvolume 14pages642651 (2018) | Download Citation

Abstract

Over the last decade, research on distinct types of CRISPR systems has revealed many structural and functional variations. Recently, several novel types of single-polypeptide CRISPR-associated systems have been discovered including Cas12a/Cpf1 and Cas13a/C2c2. Despite distant similarities to Cas9, these additional systems have unique structural and functional features, providing new opportunities for genome editing applications. Here, relevant fundamental features of natural and engineered CRISPR–Cas variants are compared. Moreover, practical matters are discussed that are essential for dedicated genome editing applications, including nuclease regulation and delivery, target specificity, as well as host repair diversity.

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Acknowledgements

J.v.d.O. is supported by the Netherlands Organization for Scientific Research (NWO) through a TOP grant (714.015.001). J.L is supported by the gravitation program from the Netherlands Organization for Scientific Research (NWO). The work of R.K. is part of the Oncode Institute which is partly financed by the Dutch Cancer Society and was funded by the gravitation program from the NWO. The work of N.G. is supported in part by Stichting Singelswim Utrecht, Stichting FSHD and TKI/Health Holland.

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Affiliations

  1. Laboratory of Microbiology, Wageningen University, Wageningen, Netherlands

    • Wen Y. Wu
    •  & John van der Oost
  2. Department of Molecular Genetics, Erasmus MC, Rotterdam, the Netherlands

    • Joyce H. G. Lebbink
    •  & Roland Kanaar
  3. Department of Radiation Oncology, Erasmus MC, Rotterdam, the Netherlands

    • Joyce H. G. Lebbink
  4. Oncode Institute, Utrecht, The Netherlands

    • Roland Kanaar
  5. Hubrecht Institute for Developmental Biology and Stem Cell Research, University Medical Center Utrecht and Faculty of Veterinary Medicine, Clinical Sciences of Companion Animals, Utrecht University, Utrecht, The Netherlands

    • Niels Geijsen

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The authors declare no competing interests.

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Correspondence to John van der Oost.

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https://doi.org/10.1038/s41589-018-0080-x