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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

作者: 左二伟;;袁堂龙;;刘敬

作者机构:

期刊名称: Nature Methods

ISSN: 1548-7091

年卷期: 2020 年 17 卷 6 期

页码:

收录情况: JCR(2021版)

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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