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DOI | 10.1126/science.aav9973 |
Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos | |
Zuo, Erwei1,2; Sun, Yidi3; Wei, Wu3,4,5; Yuan, Tanglong2; Ying, Wenqin1; Sun, Hao6; Yuan, Liyun3; Steinmetz, Lars M.4,7,8; Li, Yixue3,9,10; Yang, Hui1 | |
2019-04-19 | |
发表期刊 | SCIENCE |
ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2019 |
卷号 | 364期号:6437页码:289-+ |
文章类型 | Article |
语种 | 英语 |
国家 | Peoples R China; USA; Germany |
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. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000464956600052 |
WOS关键词 | GENOMIC DNA ; SPECIFICITIES ; REVEALS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/201240 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.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; 2.Chinese Acad Agr Sci, Ctr Anim Genom, Agr Genome Inst Shenzhen, Shenzhen 518124, Peoples R China; 3.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; 4.Stanford Univ, Stanford Genome Technol Ctr, Palo Alto, CA 94304 USA; 5.Shanghai Jiao Tong Univ, Ctr Biomed Informat, Shanghai Childrens Hosp, Shanghai 200040, Peoples R China; 6.Univ Calif San Diego, 9500 Gilman Dr, La Jolla, CA 92093 USA; 7.Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA; 8.European Mol Biol Lab, Genome Biol Unit, D-69117 Heidelberg, Germany; 9.Fudan Univ, Collaborat Innovat Ctr Genet & Dev, Shanghai 200438, Peoples R China; 10.Shanghai Ind Technol Inst, Shanghai Ctr Bioinformat Technol, Shanghai 201203, Peoples R China |
推荐引用方式 GB/T 7714 | Zuo, Erwei,Sun, Yidi,Wei, Wu,et al. Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos[J]. SCIENCE,2019,364(6437):289-+. |
APA | Zuo, Erwei.,Sun, Yidi.,Wei, Wu.,Yuan, Tanglong.,Ying, Wenqin.,...&Yang, Hui.(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-+. |
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