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Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors.

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.

SUBMITTER: Zhang M

PROVIDER: S-EPMC6532253 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors.

Zhang Meiling M Zhou Changyang C Wei Yu Y Xu Chunlong C Pan Hong H Ying Wenqin W Sun Yidi Y Sun Yun Y Xiao Qingquan Q Yao Ning N Zhong Wanxia W Li Yun Y Wu Keliang K Yuan Gao G Mitalipov Shoukhrat S Chen Zi-Jiang ZJ Yang Hui H

Genome biology 20190522 1

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 ...[more]

PMID: 31118069

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