Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors

Meiling Zhang; Changyang Zhou; Yu Wei; Chunlong Xu; Hong Pan; Wenqin Ying; Yidi Sun; Yun Sun; Qingquan Xiao; Ning Yao; Wanxia Zhong; Yun Li; Keliang Wu; Gao Yuan; Shoukhrat Mitalipov; Zi Jiang Chen; Hui Yang

doi:10.1186/s13059-019-1703-6

Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors

Meiling Zhang, Changyang Zhou, Yu Wei, Chunlong Xu, Hong Pan, Wenqin Ying, Yidi Sun, Yun Sun, Qingquan Xiao, Ning Yao, Wanxia Zhong, Yun Li, Keliang Wu, Gao Yuan, Shoukhrat Mitalipov, Zi Jiang Chen, Hui Yang

Research output: Contribution to journal › Article › peer-review

5 Scopus citations

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.

Original language	English (US)
Article number	101
Journal	Genome biology
Volume	20
Issue number	1
DOIs	https://doi.org/10.1186/s13059-019-1703-6
State	Published - May 22 2019

Keywords

Base editing
Homozygotic nucleotide substitution
Human cleaving embryos

ASJC Scopus subject areas

Ecology, Evolution, Behavior and Systematics
Genetics
Cell Biology

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Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors. / Zhang, Meiling; Zhou, Changyang; Wei, Yu; Xu, Chunlong; Pan, Hong; Ying, Wenqin; Sun, Yidi; Sun, Yun; Xiao, Qingquan; Yao, Ning; Zhong, Wanxia; Li, Yun; Wu, Keliang; Yuan, Gao; Mitalipov, Shoukhrat; Chen, Zi Jiang; Yang, Hui.

In: Genome biology, Vol. 20, No. 1, 101, 22.05.2019.

Research output: Contribution to journal › Article › peer-review

Zhang, Meiling ; Zhou, Changyang ; Wei, Yu ; Xu, Chunlong ; Pan, Hong ; Ying, Wenqin ; Sun, Yidi ; Sun, Yun ; Xiao, Qingquan ; Yao, Ning ; Zhong, Wanxia ; Li, Yun ; Wu, Keliang ; Yuan, Gao ; Mitalipov, Shoukhrat ; Chen, Zi Jiang ; Yang, Hui. / Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors. In: Genome biology. 2019 ; Vol. 20, No. 1.

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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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note = "Funding Information: This work was supported by the R&D Program of China (2018YFC2000100 and 2017YFC1001302 to HY; 2016YFC1000604 to ZJC), CAS Strategic Priority Research Program (XDB32060000), National Natural Science Foundation of China (31871502, 31522037), Shanghai Municipal Science and Technology Major Project (2018SHZDZX05), Shanghai City Committee of Science and Technology Project (18411953700, 18JC1410100), and Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetic (17DZ2271100).",

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AU - Sun, Yidi

AU - Sun, Yun

AU - Xiao, Qingquan

AU - Yao, Ning

AU - Zhong, Wanxia

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AU - Yuan, Gao

AU - Mitalipov, Shoukhrat

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N2 - 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.

AB - 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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