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Response to “Unexpected mutations after CRISPR–Cas9 editing in vivo”

Nature Methods volume 15, pages 235–236 (2018)Cite this article

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To the Editor:

We challenge the assertion of Schaefer et al.1 that Cas9 RNA-guided nuclease (RGN) genome editing results in widespread off-target mutagenesis, and question the authors' interpretation that Cas9 RGN possesses sequence-independent base-editing or indel-generating activity. We contend that the experimental design in Schaefer et al. was so significantly flawed that the conclusions presented are not supported by the data.

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References

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Acknowledgements

The authors are funded to produce mouse models using Cas9 as part of the International Mouse Phenotyping Consortium from Genome Canada and Ontario Genomics OGI-051 (L.M.J.N.), the National Human Genome Research Institute, the NIH Common Fund, through the Office of Strategic Coordination/Office of the NIH Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Cancer Institute, National Institute of Neurological Disorders and Stroke, National Institute on Deafness and Other Communication Disorders, National Institute of Environmental Health Sciences, National Institute of Drug Abuse and the Office of Research on Women's Health awards UM1HG006348 (J.D.H., J.R.S., L.T., S.D.M.B.), UM1OD023321 (L.M.J.N., K.C.L.) and UM1OD023222 (S.D.M.) and MRC IMPC Strategic Award 53658 (L.T., S.D.M.B.).

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Authors and Affiliations

  1. chairs of the IMPC Cas9 Working Group and the IMPC Steering Committee and executive director of the IMPC (),

    Lauryl M J Nutter, Steve D M Brown & Mark Moore

  2. The Centre for Phenogenomics, The Hospital for Sick Children, Toronto, Canada

    Lauryl M J Nutter

  3. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA

    Jason D Heaney & John R Seavitt

  4. Mouse Biology Program, University of California, Davis, Davis, California, USA

    K C Kent Lloyd

  5. The Jackson Laboratory, Bar Harbor, Maine, USA

    Stephen A Murray

  6. The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA

    William C Skarnes

  7. Mammalian Genetics Unit, Medical Research Center (MRC) Harwell Institute, Harwell, UK

    Lydia Teboul

  8. Mammalian Genetics Unit, Medical Research Center (MRC) Harwell Institute, Harwell, UK

    Steve D M Brown

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  1. Lauryl M J Nutter
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  2. Jason D Heaney
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  3. K C Kent Lloyd
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  4. Stephen A Murray
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  8. Steve D M Brown
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  9. Mark Moore
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Correspondence to Lauryl M J Nutter.

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The authors declare no competing financial interests.

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Nutter, L., Heaney, J., Lloyd, K. et al. Response to “Unexpected mutations after CRISPR–Cas9 editing in vivo”. Nat Methods 15, 235–236 (2018). https://doi.org/10.1038/nmeth.4559

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