期刊论文详细信息
Genome Biology
Human cleaving embryos enable robust homozygotic nucleotide substitutions by base editors
Shoukhrat Mitalipov1  Wanxia Zhong2  Meiling Zhang2  Ning Yao2  Yun Sun2  Yun Li2  Zi-jiang Chen3  Keliang Wu4  Gao Yuan4  Hong Pan5  Wenqin Ying5  Hui Yang5  Yu Wei5  Chunlong Xu5  Qingquan Xiao6  Changyang Zhou6  Yidi Sun7 
[1] 0000 0000 9758 5690, grid.5288.7, Center for Embryonic Cell and Gene Therapy, Oregon Health & Science University, 3303 Southwest, Bond Avenue, 97239, Portland, OR, USA;0000 0004 1769 9639, grid.460018.b, Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China;0000 0004 0368 8293, grid.16821.3c, Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, 200127, Shanghai, China;0000 0004 0368 8293, grid.16821.3c, Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China;Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, 200127, Shanghai, China;0000 0004 1769 9639, grid.460018.b, Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China;National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China;The Key laboratory for Reproductive Endocrinology of Ministry of Education, 250021, Jinan, Shandong, China;0000 0004 1769 9639, grid.460018.b, Center for Reproductive Medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, China;National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Jinan, China;The Key laboratory for Reproductive Endocrinology of Ministry of Education, 250021, Jinan, Shandong, China;0000000119573309, grid.9227.e, 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, 200031, Shanghai, China;0000000119573309, grid.9227.e, 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, 200031, Shanghai, China;0000 0004 1797 8419, grid.410726.6, College of Life Sciences, University of Chinese Academy of Sciences, 100049, Beijing, China;0000000119573309, grid.9227.e, Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031, Shanghai, China;
关键词: Base editing;    Human cleaving embryos;    Homozygotic nucleotide substitution;   
DOI  :  10.1186/s13059-019-1703-6
来源: publisher
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【 摘 要 】

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】

CC BY   

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