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Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors

Published on Dec 1, 2019in Genome Biology14.03
· DOI :10.1186/s13059-019-1703-6
Meiling Zhang5
Estimated H-index: 5
(SJTU: Shanghai Jiao Tong University),
Changyang Zhou5
Estimated H-index: 5
(CAS: Chinese Academy of Sciences)
+ 14 AuthorsHui Yang19
Estimated H-index: 19
(CAS: Chinese Academy of Sciences)
Abstract
Base editing installs a precise nucleotide change in specific gene loci without causing a double-strand break. Its efficiency in human embryos is generally low, limiting its utility in functional genetic studies. Here, we report that injecting base editors into human cleaving two-cell and four-cell embryos results in much higher (up to 13-fold) homozygotic nucleotide substitution efficiency as opposed to MII oocytes or zygotes. Furthermore, as a proof-of-principle study, a point mutation can be efficiently corrected by our method. Our study indicates that human cleaving embryos provide an efficient base editing window for robust gene disruption and correction.
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