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

Nature Methods volume 15, pages 236–237 (2018)Cite this article

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To the Editor:

The recent correspondence by Schaefer et al.1 contradicts numerous publications in the field using similar analytical approaches and methods2, some performed in human induced pluripotent stem cell (iPSC) and embryonic stem cell (ESC) lines3,4. The authors suggest that the CRISPR–Cas9 system is mutagenic in genomic regions not expected to be targeted by the gRNA. We believe that the conclusions drawn in this work are not substantiated by the data presented. It is impossible to ascribe the observed differences in the subject mice to the effects of CRISPR–Cas9 per se. The genetic differences seen in this comparative study were likely present before editing with CRISPR–Cas9.

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References

  1. Schaefer, K.A. et al. Nat. Methods 14, 547–548 (2017).

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  2. Iyer, V. et al. Nat. Methods 12, 479 (2015).

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Author notes

  1. George M Church

    Present address: Harvard Medical School, Boston, Massachusetts, USA

  2. Luis A Barrera

    Present address: Arrakis Therapeutics, Waltham, Massachusetts, USA

Authors and Affiliations

  1. Editas Medicine, Cambridge, Massachusetts, USA

    Christopher J Wilson, Anne Bothmer, Morgan L Maeder, Deepak Reyon, Cecilia Cotta-Ramusino, Cecilia A Fernandez, Eugenio Marco, Luis A Barrera, Hariharan Jayaram, Charles F Albright, Gerald F Cox & Vic E Myer

  2. Fulcrum Genomics, Somerville, Massachusetts, USA

    Tim Fennell

Authors
  1. Christopher J Wilson
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  2. Tim Fennell
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  3. Anne Bothmer
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  4. Morgan L Maeder
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  5. Deepak Reyon
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  6. Cecilia Cotta-Ramusino
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  8. Eugenio Marco
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  9. Luis A Barrera
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  10. Hariharan Jayaram
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  11. Charles F Albright
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  12. Gerald F Cox
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  13. George M Church
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  14. Vic E Myer
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Corresponding author

Correspondence to Vic E Myer.

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Competing interests

A.B., M.L.M., D.R., C.J.W., C.C.-R., C.A.F., E.M., L.A.B., H.J., C.F.A., G.F.C. and V.E.M. are full-time employees of Editas Medicine. T.F. is a paid consultant of Editas Medicine. G.M.C. is an advisor to Editas Medicine, and his competing interests are covered here: http://arep.med.harvard.edu/gmc/

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Wilson, C., Fennell, T., Bothmer, A. et al. Response to “Unexpected mutations after CRISPR–Cas9 editing in vivo”. Nat Methods 15, 236–237 (2018). https://doi.org/10.1038/nmeth.4552

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