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

Zuo, Erwei; Sun, Yidi; Yuan, Tanglong; He, Bingbing; Zhou, Changyang; Ying, Wenqin; Liu, Jing; Wei, Wu et al. · Nat Methods · 2020

basic_science · Level V

Where this comes from

Abstract

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.

Medical subject headings