A rationally engineered cytosine base editor retains high on-target activity while reducing both DNA and RNA off-target effects

文献类型： 外文期刊

第一作者： Zuo, Erwei

作者： Zuo, Erwei;Yuan, Tanglong;Liu, Jing;Zuo, Erwei;He, Bingbing;Zhou, Changyang;Ying, Wenqin;Yang, Hui;Sun, Yidi;Zeng, Rong;Sun, Yidi;Wei, Wu;Li, Yixue;Wei, Wu;Zeng, Rong;Li, Yixue;Li, Yixue;Li, Yixue;Yang, Hui

作者机构：

期刊名称：NATURE METHODS （ 影响因子：28.547； 五年影响因子：44.96 ）

ISSN： 1548-7091

年卷期： 2020 年 17 卷 6 期

页码：

收录情况： SCI

摘要： Cytosine base editors (CBEs) offer a powerful tool for correcting point mutations, yet their DNA and RNA off-target activities have caused concerns in biomedical applications. We describe screens of 23 rationally engineered CBE variants, which reveal mutation residues in the predicted DNA-binding site can dramatically decrease the Cas9-independent off-target effects. Furthermore, we obtained a CBE variant-YE1-BE3-FNLS-that retains high on-target editing efficiency while causing extremely low off-target edits and bystander edits. Structural and biochemical insights help engineer a cytosine base editor variant that possesses improved on-target activity with minimal DNA and RNA off-target editing.

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