Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors

Genome Biology

Shoukhrat Mitalipov¹  Ning Yao²  Wanxia Zhong²  Yun Li²  Meiling Zhang²  Zi-jiang Chen²  Yun Sun²  Keliang Wu³  Gao Yuan³  Chunlong Xu⁴  Qingquan Xiao⁴  Hui Yang⁴  Hong Pan⁴  Yu Wei⁴  Changyang Zhou⁴  Wenqin Ying⁴  Yidi Sun⁵ 

[1] Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University;Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University;Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University;Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences;Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences;

关键词: Base editing;    Human cleaving embryos;    Homozygotic nucleotide substitution;   

DOI  :  10.1186/s13059-019-1703-6

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown