Correspondence | Published:

Unexpected mutations after CRISPR–Cas9 editing in vivo

Nature Methods volume 14, pages 547548 (2017) | Download Citation

  • This article was retracted on 27 April 2018
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  • Updated online 14 June 2017

    Editorial Note: readers are alerted that the conclusions of this paper are subject to criticisms that are being considered by editors. A further editorial response will follow the resolution of these issues.

  • Corrected online 25 July 2017

    Editorial Expression of Concern: The editors of Nature Methods are issuing an editorial expression of concern regarding this paper to alert our readers to concerns about interpretation of the data. Multiple groups have questioned the interpretation that single nucleotide changes seen in whole-genome sequences of two CRISPR–Cas9-treated mice are due to the CRISPR treatment. Since the background genetic variation between the control mouse and the CRISPR-treated animals is not known, an alternative proposed interpretation is that the observed changes are due to normal genetic variation. We are in contact with the critics and with the authors to examine this matter further. We will update our readers once these investigations are complete. All the authors do not agree with the journal's decision to issue an editorial expression of concern.

  • Retracted online 30 March 2018

    This paper is being retracted because the genomic variants observed by the authors in two CRISPR-treated mice cannot be conclusively attributed to CRISPR–Cas9. The paper was a peer-reviewed Correspondence in the journal. The authors made their observation as part of their work on correction of a gene involved in blindness. The authors used mice of the inbred FVB/NJ strain from the JAX genetic quality control program that were purchased within months of each other and that were not bred in the authors' laboratory. The assumption was that this design was sufficient to control for genetic variation in an inbred strain. Since publication of the work, however, it has been brought to the journal's and the authors' attention that without parental controls or more analysis of genetic background, it is not certain that the variants reported are due to CRISPR treatment (https://doi.org/10.1038/nmeth.4559, https://doi.org/10.1038/nmeth.4552, https://doi.org/10.1038/nmeth.4553, https://doi.org/10.1038/nmeth.4541, https://doi.org/10.1038/nmeth.4554). The study is therefore being retracted to maintain the accuracy of the scientific record.  S.H.T. and W.-H.W. agree with the retraction. K.A.S., D.F.C., A.G.B. and V.B.M. do not agree with the retraction. All authors note that there is very little whole-genome sequencing data on the effects of CRISPR treatment in vivo. The question of whether CRISPR has effects on the in vivo genome will require further study; the authors are carrying out follow-up studies using whole-genome sequencing.

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Acknowledgements

We acknowledge the efforts and expertise of the New York Genome Center. S. Wu assisted with data analysis. K.A.S. is supported by NIH grant F31EY026789. V.B.M. and A.G.B. are supported by NIH grants (R01EY026682, R01EY024665, R01EY025225, R01EY024698, R01NS098590 and R21AG050437) and Research to Prevent Blindness (RPB), New York, New York. The Bernard & Shirlee Brown Glaucoma Laboratory is supported by NIH grants (5P30EY019007, R01EY018213). The National Cancer Institute Core is supported by an NIH grant (5P30CA013696), the RPB Physician-Scientist Award, and unrestricted funds from RPB, New York, New York, USA. S.H.T. is a member of the RD-CURE Consortium and is supported by the Tistou and Charlotte Kerstan Foundation, the Schneeweiss Stem Cell Fund, New York State (grant C029572), the Crowley Family Fund, and the Gebroe Family Foundation.

Author information

Author notes

    • Kellie A Schaefer
    •  & Wen-Hsuan Wu

    These authors contributed equally to this work.

Affiliations

  1. Omics Laboratory, Stanford University, Palo Alto, California, USA.

    • Kellie A Schaefer
    • , Diana F Colgan
    •  & Vinit B Mahajan
  2. Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, Iowa, USA.

    • Kellie A Schaefer
  3. Jonas Children's Vision Care and Bernard & Shirlee Brown Glaucoma Laboratory, Departments of Ophthalmology, Pathology & Cell Biology, Institute of Human Nutrition, College of Physicians and Surgeons, Columbia University, New York, New York, USA.

    • Wen-Hsuan Wu
    •  & Stephen H Tsang
  4. Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, New York, USA.

    • Wen-Hsuan Wu
    •  & Stephen H Tsang
  5. Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.

    • Alexander G Bassuk
  6. Department of Neurology, University of Iowa, Iowa City, Iowa, USA.

    • Alexander G Bassuk
  7. Byers Eye Institute, Stanford University, Palo Alto, CA, USA

    • Vinit B Mahajan

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Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Alexander G Bassuk or Vinit B Mahajan.

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DOI

https://doi.org/10.1038/nmeth.4293

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