Expanding C-T base editing toolkit with diversified cytidine deaminases

被引：61
作者：
Cheng, Tian-Lin [1 ]
Li, Shuo [2 ]
Yuan, Bo [1 ]
Wang, Xiaolin [2 ,3 ]
Zhou, Wenhao [4 ]
Qiu, Zilong [1 ]
机构：
[1] Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Inst Neurosci, State Key Lab Neurosci, Shanghai 200031, Peoples R China
[2] Fudan Univ, Zhongshan Hosp, Dept Intervent Radiol, 180 Fenglin Rd, Shanghai 200032, Peoples R China
[3] Shanghai Inst Med Imaging, Shanghai 200032, Peoples R China
[4] Fudan Univ, Dept Neonatol, Childrens Hosp, Shanghai 201102, Peoples R China
来源：
NATURE COMMUNICATIONS | 2019年 / 10卷 / 1期
基金：
中国国家自然科学基金;
关键词：
READ ALIGNMENT; GENOMIC DNA; CRISPR-CAS9;
D O I：
10.1038/s41467-019-11562-6
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
引用
收藏
页数：10
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