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Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos

文献类型：期刊论文

作者Zuo, Erwei2,3; Ying, Wenqin2; Yang, Hui2; Yuan, Tanglong3; Sun, Yidi4; Wei, Wu4; Yuan, Liyun4; Li, Yixue4; Wei, Wu5,6; Steinmetz, Lars M.5
刊名SCIENCE
出版日期2019
卷号364期号:6437页码:289-+
ISSN号0036-8075
DOI10.1126/science.aav9973
文献子类Article
英文摘要Genome editing holds promise for correcting pathogenic mutations. However, it is difficult to determine off-target effects of editing due to single-nucleotide polymorphism in individuals. Here we developed a method named GOTI (genome-wide off-target analysis by two-cell embryo injection) to detect off-target mutations by editing one blastomere of two-cell mouse embryos using either CRISPR-Cas9 or base editors. Comparison of the whole-genome sequences of progeny cells of edited and nonedited blastomeres at embryonic day 14.5 showed that off-target single-nucleotide variants (SNVs) were rare in embryos edited by CRISPR-Cas9 or adenine base editor, with a frequency close to the spontaneous mutation rate. By contrast, cytosine base editing induced SNVs at more than 20-fold higher frequencies, requiring a solution to address its fidelity.
学科主题Science & Technology - Other Topics
WOS关键词GENOMIC DNA ; SPECIFICITIES ; REVEALS
语种英语
出版者AMER ASSOC ADVANCEMENT SCIENCE
WOS记录号WOS:000464956600052
版本出版稿
源URL[http://202.127.25.144/handle/331004/595]  
专题中国科学院上海生命科学研究院营养科学研究所
作者单位1.Shanghai Ind Technol Inst, Shanghai Ctr Bioinformat Technol, Shanghai 201203, Peoples R China,
2.Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Key Lab Primate Neurobiol,Shanghai Res Ctr Brain, Shanghai Inst Biol Sci,Inst Neurosci,State Key La, Shanghai 200031, Peoples R China;
3.Chinese Acad Agr Sci, Ctr Anim Genom, Agr Genome Inst Shenzhen, Shenzhen 518124, Peoples R China;
4.Chinese Acad Sci, Univ Chinese Acad Sci, CAS MPG Partner Inst Computat Biol, Shanghai Inst Biol Sci,Key Lab Computat Biol, Shanghai 200031, Peoples R China;
5.Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA;
6.Shanghai Jiao Tong Univ, Ctr Biomed Informat, Shanghai Childrens Hosp, Shanghai 200040, Peoples R China;
7.Univ Calif San Diego, 9500 Gilman Dr, La Jolla, CA 92093 USA;
8.Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA;
9.European Mol Biol Lab, Genome Biol Unit, D-69117 Heidelberg, Germany;
10.Fudan Univ, Collaborat Innovat Ctr Genet & Dev, Shanghai 200438, Peoples R China;
推荐引用方式
GB/T 7714		 Zuo, Erwei,Ying, Wenqin,Yang, Hui,et al. Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos[J]. SCIENCE,2019,364(6437):289-+.
APA Zuo, Erwei.,Ying, Wenqin.,Yang, Hui.,Yuan, Tanglong.,Sun, Yidi.,...&,.(2019).Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos.SCIENCE,364(6437),289-+.
MLA Zuo, Erwei,et al."Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos".SCIENCE 364.6437(2019):289-+.

入库方式： OAI收割

来源：上海营养与健康研究所

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