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Expanding C-T base editing toolkit with diversified cytidine deaminases.

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.

SUBMITTER: Cheng TL

PROVIDER: S-EPMC6689024 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Expanding C-T base editing toolkit with diversified cytidine deaminases.

Cheng Tian-Lin TL Li Shuo S Yuan Bo B Wang Xiaolin X Zhou Wenhao W Qiu Zilong Z

Nature communications 20190809 1

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 e ...[more]

PMID: 31399578

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