BE-PLUS: a new base editing tool with broadened editing window and enhanced fidelity

被引：100

作者：

Jiang, Wen ^{[1
]}

Feng, Songjie ^{[2
,3
,4
]}

Huang, Shisheng ^{[2
]}

Yu, Wenxia ^{[2
]}

Li, Guanglei ^{[2
]}

Yang, Guang ^{[2
]}

Liu, Yajing ^{[2
,3
,4
]}

Zhang, Yu ^{[2
]}

Zhang, Lei ^{[3
,4
]}

Hou, Yu ^{[1
]}

Chen, Jia ^{[2
]}

Chen, Jieping ^{[1
]}

Huang, Xingxu ^{[2
]}

机构：

[1] Army Med Univ, Mil Med Univ 3, Southwest Hosp, Dept Hematol, Chongqing 400038, Peoples R China

[2] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China

[3] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[4] Chinese Acad Sci, Shanghai Inst Biol Sci, Shanghai 201210, Peoples R China

来源：

CELL RESEARCH | 2018年 / 28卷 / 08期

基金：

美国国家科学基金会;

关键词：

MAMMALIAN-CELLS; DEAMINASE FUSIONS; HUMAN EMBRYOS; TARGET BASE; GENOME; DNA; PROTEIN; SYSTEM; HYPERMUTATION; MUTATIONS;

D O I：

10.1038/s41422-018-0052-4

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Base editor (BE), containing a cytidine deaminase and catalytically defective Cas9, has been widely used to perform base editing. However, the narrow editing window of BE limits its utility. Here, we developed a new editing technology named as base editor for programming larger C to U (T) scope (BE-PLUS) by fusing 10 copies of GCN4 peptide to nCas9(D10A) for recruiting scFv-APOBEC-UGI-GB1 to the target sites. The new system achieves base editing with a broadened window, resulting in an increased genome-targeting scope. Interestingly, the new system yielded much fewer unwanted indels and non-C-to-T conversions. We also demonstrated its potential use in gene disruption across the whole genome through induction of stop codons (iSTOP). Taken together, the BE-PLUS system offers a new editing tool with increased editing window and enhanced fidelity.

引用

页码：855 / 861

页数：7

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