Single C-to-T substitution using engineered APOBEC3G-nCas9 base editors with minimum genome- and transcriptome-wide off-target effects

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dc.citation.articleNumbereaba1773en_US
dc.citation.issueNumber29en_US
dc.citation.journalTitleScience Advancesen_US
dc.citation.volumeNumber6en_US
dc.contributor.authorLee, Sangsinen_US
dc.contributor.authorDing, Ningen_US
dc.contributor.authorSun, Yidien_US
dc.contributor.authorYuan, Tanglongen_US
dc.contributor.authorLi, Jingen_US
dc.contributor.authorYuan, Qichenen_US
dc.contributor.authorLiu, Lizhongen_US
dc.contributor.authorYang, Jieen_US
dc.contributor.authorWang, Qianen_US
dc.contributor.authorKolomeisky, Anatoly B.en_US
dc.contributor.authorHilton, Isaac B.en_US
dc.contributor.authorZuo, Erweien_US
dc.contributor.authorGao, Xueen_US
dc.contributor.orgCenter for Theoretical and Biological Physicsen_US
dc.date.accessioned2020-10-30T19:43:45Zen_US
dc.date.available2020-10-30T19:43:45Zen_US
dc.date.issued2020en_US
dc.description.abstractCytosine base editors (CBEs) enable efficient cytidine-to-thymidine (C-to-T) substitutions at targeted loci without double-stranded breaks. However, current CBEs edit all Cs within their activity windows, generating undesired bystander mutations. In the most challenging circumstance, when a bystander C is adjacent to the targeted C, existing base editors fail to discriminate them and edit both Cs. To improve the precision of CBE, we identified and engineered the human APOBEC3G (A3G) deaminase; when fused to the Cas9 nickase, the resulting A3G-BEs exhibit selective editing of the second C in the 5′-CC-3′ motif in human cells. Our A3G-BEs could install a single disease-associated C-to-T substitution with high precision. The percentage of perfectly modified alleles is more than 6000-fold for disease correction and more than 600-fold for disease modeling compared with BE4max. On the basis of the two-cell embryo injection method and RNA sequencing analysis, our A3G-BEs showed minimum genome- and transcriptome-wide off-target effects, achieving high targeting fidelity.en_US
dc.identifier.citationLee, Sangsin, Ding, Ning, Sun, Yidi, et al.. "Single C-to-T substitution using engineered APOBEC3G-nCas9 base editors with minimum genome- and transcriptome-wide off-target effects." <i>Science Advances,</i> 6, no. 29 (2020) American Association for the Advancement of Science: https://doi.org/10.1126/sciadv.aba1773.en_US
dc.identifier.doihttps://doi.org/10.1126/sciadv.aba1773en_US
dc.identifier.urihttps://hdl.handle.net/1911/109465en_US
dc.language.isoengen_US
dc.publisherAmerican Association for the Advancement of Scienceen_US
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.en_US
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/en_US
dc.titleSingle C-to-T substitution using engineered APOBEC3G-nCas9 base editors with minimum genome- and transcriptome-wide off-target effectsen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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