Unexpected mutations after CRISPR-Cas9 editing in vivo

Kellie A Schaefer^{1

2}, Wen-Hsuan Wu^{3

4}, Diana F Colgan¹, Stephen H Tsang^{3

4}, Alexander G Bassuk^{5

6}, Vinit B Mahajan^{1

7}

Affiliations

¹ Omics Laboratory, Stanford University, Palo Alto, California, USA.
² Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, Iowa, USA.
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.
⁴ Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, New York, USA.
⁵ Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
⁶ Department of Neurology, University of Iowa, Iowa City, Iowa, USA.
⁷ Byers Eye Institute, Stanford University, Palo Alto, CA, USA.

PMID: 28557981
PMCID: PMC5796662
DOI: 10.1038/nmeth.4293

Unexpected mutations after CRISPR-Cas9 editing in vivo

Kellie A Schaefer et al. Nat Methods. 2017.

. 2017 May 30;14(6):547-548.

doi: 10.1038/nmeth.4293.

Authors

Kellie A Schaefer^{1

2}, Wen-Hsuan Wu^{3

4}, Diana F Colgan¹, Stephen H Tsang^{3

4}, Alexander G Bassuk^{5

6}, Vinit B Mahajan^{1

7}

Affiliations

¹ Omics Laboratory, Stanford University, Palo Alto, California, USA.
² Interdisciplinary Graduate Program in Genetics, University of Iowa, Iowa City, Iowa, USA.
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.
⁴ Edward S. Harkness Eye Institute, New York-Presbyterian Hospital, New York, New York, USA.
⁵ Department of Pediatrics, University of Iowa, Iowa City, Iowa, USA.
⁶ Department of Neurology, University of Iowa, Iowa City, Iowa, USA.
⁷ Byers Eye Institute, Stanford University, Palo Alto, CA, USA.

PMID: 28557981
PMCID: PMC5796662
DOI: 10.1038/nmeth.4293

No abstract available

PubMed Disclaimer

Conflict of interest statement

COMPETING FINANCIAL INTERESTS

The authors declare no competing financial interests.

Figures

**Figure 1**
CRISPR gene correction introduces an unexpectedly high number of mutations in a mouse model of gene therapy. (a) Venn diagrams display SNVs detected in WGS data by the indicated bioinformatics tools. (b) Summary of variant types found in mouse F03, mouse F05, and shared between both mice.

See this image and copyright information in PMC

Comment in

Response to "Unexpected mutations after CRISPR-Cas9 editing in vivo".
Lescarbeau RM, Murray B, Barnes TM, Bermingham N. Lescarbeau RM, et al. Nat Methods. 2018 Apr;15(4):237. doi: 10.1038/nmeth.4553. Epub 2018 Mar 30. Nat Methods. 2018. PMID: 29600988 No abstract available.
Response to "Unexpected mutations after CRISPR-Cas9 editing in vivo".
Wilson CJ, Fennell T, Bothmer A, Maeder ML, Reyon D, Cotta-Ramusino C, Fernandez CA, Marco E, Barrera LA, Jayaram H, Albright CF, Cox GF, Church GM, Myer VE. Wilson CJ, et al. Nat Methods. 2018 Apr;15(4):236-237. doi: 10.1038/nmeth.4552. Epub 2018 Mar 30. Nat Methods. 2018. PMID: 29600989 No abstract available.
Response to "Unexpected mutations after CRISPR-Cas9 editing in vivo".
Kim ST, Park J, Kim D, Kim K, Bae S, Schlesner M, Kim JS. Kim ST, et al. Nat Methods. 2018 Apr;15(4):239-240. doi: 10.1038/nmeth.4554. Epub 2018 Mar 30. Nat Methods. 2018. PMID: 29600990 No abstract available.
Response to "Unexpected mutations after CRISPR-Cas9 editing in vivo".
Nutter LMJ, Heaney JD, Lloyd KCK, Murray SA, Seavitt JR, Skarnes WC, Teboul L, Brown SDM, Moore M. Nutter LMJ, et al. Nat Methods. 2018 Apr;15(4):235-236. doi: 10.1038/nmeth.4559. Epub 2018 Mar 30. Nat Methods. 2018. PMID: 29600991 No abstract available.
Response to "Unexpected mutations after CRISPR-Cas9 editing in vivo".
Lareau CA, Clement K, Hsu JY, Pattanayak V, Joung JK, Aryee MJ, Pinello L. Lareau CA, et al. Nat Methods. 2018 Apr;15(4):238-239. doi: 10.1038/nmeth.4541. Epub 2018 Mar 30. Nat Methods. 2018. PMID: 29600992 Free PMC article. No abstract available.

References

1. Wu WH, et al. CRISPR repair reveals causative mutation in a preclinical model of retinitis pigmentosa. Mol Ther. 2016;24:1388–1394. - PMC - PubMed
1. Koo T, Lee J, Kim JS. Measuring and reducing off-target activities of programmable nucleases including CRISPR–Cas9. Mol Cells. 2015;38:475–481. - PMC - PubMed
1. Iyer V, et al. Off-target mutations are rare in Cas9-modified mice. Nat Methods. 2015;12:479. - PubMed
1. Nachman MW, Crowell SL. Estimate of the mutation rate per nucleotide in humans. Genetics. 2000;156:297–304. - PMC - PubMed
1. Roach JC, et al. Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science. 2010;328:636–639. - PMC - PubMed

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Unexpected mutations after CRISPR-Cas9 editing in vivo

Affiliations

Unexpected mutations after CRISPR-Cas9 editing in vivo

Authors

Affiliations

Conflict of interest statement

Figures

Comment in

References

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