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 Zhang2
Estimated H-index: 2
(SJTU: Shanghai Jiao Tong University),
Changyang Zhou3
Estimated H-index: 3
(CAS: Chinese Academy of Sciences)
+ 14 AuthorsHui Yang16
Estimated H-index: 16
(CAS: Chinese Academy of Sciences)
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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#1Erwei Zuo (CAS: Chinese Academy of Sciences)H-Index: 3
#2Yidi Sun (CAS-MPG Partner Institute for Computational Biology)H-Index: 7
Last.Hui Yang (CAS: Chinese Academy of Sciences)H-Index: 16
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#1Shuai Jin (CAS: Chinese Academy of Sciences)H-Index: 3
#2Yuan Zong (CAS: Chinese Academy of Sciences)H-Index: 6
Last.Feng Zhang (UMN: University of Minnesota)H-Index: 104
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#1Yanting Zeng (Guangzhou Medical University)H-Index: 2
#2Jianan Li (ShanghaiTech University)H-Index: 8
Last.Xingxu Huang (CAS: Chinese Academy of Sciences)H-Index: 14
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#1Puping Liang (SYSU: Sun Yat-sen University)H-Index: 7
#2Chenhui Ding (SYSU: Sun Yat-sen University)H-Index: 14
Last.Yongxiang Liu (SYSU: Sun Yat-sen University)H-Index: 1
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#1Guanglei Li (Guangzhou Medical University)H-Index: 4
#2Yajing Liu (ShanghaiTech University)H-Index: 6
Last.Xingxu Huang (ShanghaiTech University)H-Index: 14
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#1Changyang Zhou (CAS: Chinese Academy of Sciences)H-Index: 3
#2Meiling Zhang (SJTU: Shanghai Jiao Tong University)H-Index: 2
Last.Weiping Li (SJTU: Shanghai Jiao Tong University)H-Index: 7
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#1Hong Ma (Oregon National Primate Research Center)H-Index: 27
#2Nuria Marti-Gutierrez (OHSU: Oregon Health & Science University)H-Index: 1
Last.Riffat Ahmed (OHSU: Oregon Health & Science University)H-Index: 10
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