Match!

Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos

Published on Feb 28, 2019in Science41.037
· DOI :10.1126/science.aav9973
Erwei Zuo6
Estimated H-index: 6
(CAS: Chinese Academy of Sciences),
Yidi Sun8
Estimated H-index: 8
(CAS-MPG Partner Institute for Computational Biology)
+ 7 AuthorsHui Yang19
Estimated H-index: 19
(CAS: Chinese Academy of Sciences)
Sources
Abstract
Genome editing holds promise for correcting pathogenic mutations. However, it is difficult to determine off-target effects of editing due to single nucleotide polymorphism in individuals. Here, we developed a method named GOTI (Genome-wide Off-target analysis by Two-cell embryo Injection) to detect off-target mutations by editing one blastomere of two-cell mouse embryos using either CRISPR-Cas9 or base editors. Comparison of the whole genome sequences of progeny cells of edited vs. non-edited blastomeres at E14.5 showed that off-target single nucleotide variants (SNVs) were rare in embryos edited by CRISPR-Cas9 or adenine base editor, with a frequency close to the spontaneous mutation rate. In contrast, cytosine base editing induced SNVs with over 20-fold higher frequencies, requiring a solution to address its fidelity.
  • References (33)
  • Citations (66)
📖 Papers frequently viewed together
201643.07Nature
5 Authors (Alexis C. Komor, ..., David R. Liu)
866 Citations
201743.07Nature
457 Citations
201941.04Science
11 Authors (Shuai Jin, ..., Caixia Gao)
55 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
References33
Newest
Cited By66
Newest