Journal
NATURE METHODS
Volume 15, Issue 7, Pages 512-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41592-018-0011-5
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Funding
- Genentech, a member of the Roche Group
- NIH/NHGRI grant [5U41HG002371-15]
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Despite widespread use of CRISPR, comprehensive data on the frequency and impact of Cas9-mediated off-targets in modified rodents are limited. Here we present deep-sequencing data from 81 genome-editing projects on mouse and rat genomes at 1,423 predicted off-target sites, 32 of which were confirmed, and show that high-fidelity Cas9 versions reduced off-target mutation rates in vivo. Using whole-genome sequencing data from ten mouse embryos, treated with a single guide RNA (sgRNA), and from their genetic parents, we found 43 off-targets, 30 of which were predicted by an adapted version of GUIDE-seq.
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