Expanding C–T base editing toolkit with diversified cytidine deaminases

Tian-Lin Cheng (), Shuo Li, Bo Yuan, Xiaolin Wang, Wenhao Zhou and Zilong Qiu ()
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Tian-Lin Cheng: Chinese Academy of Sciences
Shuo Li: Zhongshan Hospital, Fudan University
Bo Yuan: Chinese Academy of Sciences
Xiaolin Wang: Zhongshan Hospital, Fudan University
Wenhao Zhou: Children’s Hospital of Fudan University
Zilong Qiu: Chinese Academy of Sciences

Nature Communications, 2019, vol. 10, issue 1, 1-10

Abstract: Abstract Base editing tools for cytosine to thymine (C–T) conversion enable genome manipulation at single base-pair resolution with high efficiency. Available base editors (BEs) for C–T conversion (CBEs) have restricted editing scopes and nonnegligible off-target effects, which limit their applications. Here, by screening diversified lamprey cytidine deaminases, we establish various CBEs with expanded and diversified editing scopes, which could be further refined by various fusing strategies, fusing at either N-terminus or C–terminus of nCas9. Furthermore, off-target analysis reveals that several CBEs display improved fidelity. Our study expands the toolkits for C–T conversion, serves as guidance for appropriate choice and offers a framework for benchmarking future improvement of base editing tools.

Date: 2019
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DOI: 10.1038/s41467-019-11562-6

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