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dc.contributor.authorLee, Sangsin
Ding, Ning
Sun, Yidi
Yuan, Tanglong
Li, Jing
Yuan, Qichen
Liu, Lizhong
Yang, Jie
Wang, Qian
Kolomeisky, Anatoly B.
Hilton, Isaac B.
Zuo, Erwei
Gao, Xue
dc.date.accessioned 2020-10-30T19:43:45Z
dc.date.available 2020-10-30T19:43:45Z
dc.date.issued 2020
dc.identifier.citation Lee, 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." Science Advances, 6, no. 29 (2020) American Association for the Advancement of Science: https://doi.org/10.1126/sciadv.aba1773.
dc.identifier.urihttps://hdl.handle.net/1911/109465
dc.description.abstract Cytosine 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.
dc.language.iso eng
dc.publisher American Association for the Advancement of Science
dc.rights This 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.
dc.rights.urihttps://creativecommons.org/licenses/by-nc/4.0/
dc.title Single C-to-T substitution using engineered APOBEC3G-nCas9 base editors with minimum genome- and transcriptome-wide off-target effects
dc.type Journal article
dc.citation.journalTitle Science Advances
dc.contributor.org Center for Theoretical and Biological Physics
dc.citation.volumeNumber 6
dc.citation.issueNumber 29
dc.type.dcmi Text
dc.identifier.doihttps://doi.org/10.1126/sciadv.aba1773
dc.type.publication publisher version
dc.citation.articleNumber eaba1773


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