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The experimental design and data interpretation in “Unexpected mutations after CRISPR–Cas9 editing in vivo” by Schaefer et al. are insufficient to support the conclusions drawn by the authors

Christopher J. Wilson, Tim Fennell, 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, George M. Church, Vic E. Myer
doi: https://doi.org/10.1101/153338
Christopher J. Wilson
1Editas Medicine, 11 Hurley Street, Cambridge, MA 02141
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Tim Fennell
2Fulcrum Genomics, 411A Highland Ave #372, Somerville MA 02144
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Anne Bothmer
1Editas Medicine, 11 Hurley Street, Cambridge, MA 02141
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Morgan L. Maeder
1Editas Medicine, 11 Hurley Street, Cambridge, MA 02141
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Deepak Reyon
1Editas Medicine, 11 Hurley Street, Cambridge, MA 02141
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Cecilia Cotta-Ramusino
1Editas Medicine, 11 Hurley Street, Cambridge, MA 02141
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Cecilia A. Fernandez
1Editas Medicine, 11 Hurley Street, Cambridge, MA 02141
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Eugenio Marco
1Editas Medicine, 11 Hurley Street, Cambridge, MA 02141
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Luis A. Barrera
1Editas Medicine, 11 Hurley Street, Cambridge, MA 02141
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Hariharan Jayaram
1Editas Medicine, 11 Hurley Street, Cambridge, MA 02141
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Charles F. Albright
1Editas Medicine, 11 Hurley Street, Cambridge, MA 02141
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Gerald F. Cox
1Editas Medicine, 11 Hurley Street, Cambridge, MA 02141
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George M. Church
3Harvard Medical School, Boston, MA, USA
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Vic E. Myer
1Editas Medicine, 11 Hurley Street, Cambridge, MA 02141
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Abstract

The recent correspondence to the Editor of Nature Methods by Schaefer et. al.1 has garnered significant attention since its publication as a result of its strong conclusions contradicting numerous publications in the field using similar analytical approaches and methods2-4. The authors suggest that the CRISPR-Cas9 system is highly mutagenic in genomic regions not expected to be targeted by the gRNA. We believe that the conclusions drawn from this study are unsubstantiated by the disclosed experiments as they were designed and carried out. Further, it is impossible to ascribe the observed differences in the subject mice to the effects of CRISPR per se. The genetic differences seen in this comparative analysis were likely present prior to editing with CRISPR.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 21, 2017.
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The experimental design and data interpretation in “Unexpected mutations after CRISPR–Cas9 editing in vivo” by Schaefer et al. are insufficient to support the conclusions drawn by the authors
Christopher J. Wilson, Tim Fennell, 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, George M. Church, Vic E. Myer
bioRxiv 153338; doi: https://doi.org/10.1101/153338
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The experimental design and data interpretation in “Unexpected mutations after CRISPR–Cas9 editing in vivo” by Schaefer et al. are insufficient to support the conclusions drawn by the authors
Christopher J. Wilson, Tim Fennell, 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, George M. Church, Vic E. Myer
bioRxiv 153338; doi: https://doi.org/10.1101/153338

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