Efficient base editing with high precision in rabbits using YFE-BE4max

被引：37

作者：

Liu, Zhiquan ^{[1
]}

Chen, Siyu ^{[1
]}

Shan, Huanhuan ^{[1
]}

Jia, Yingqi ^{[1
]}

Chen, Mao ^{[1
]}

Song, Yuning ^{[1
]}

Lai, Liangxue ^{[1
,2
,3
,4
]}

Li, Zhanjun ^{[1
]}

机构：

[1] Jilin Univ, Coll Anim Sci, Key Lab Zoonosis Res, Minist Educ, Changchun 130062, Peoples R China

[2] Chinese Acad Sci, Guangzhou Inst Biomed & Hlth, Guangdong Prov Key Lab Stem Cell & Regenerat Med, CAS Key Lab Regenerat Biol,South China Inst Stem, Guangzhou 510530, Guangdong, Peoples R China

[3] Guangzhou Regenerat Med & Hlth Guang Dong Lab GRM, Guangzhou 510005, Peoples R China

[4] Chinese Acad Sci, Inst Stem Cell & Regenerat, Beijing 100101, Peoples R China

来源：

CELL DEATH & DISEASE | 2020年 / 11卷 / 01期

关键词：

GENE; DNA;

D O I：

10.1038/s41419-020-2244-3

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Cytidine base editors, composed of a cytidine deaminase fused to Cas9 nickase, enable efficient C-to-T conversion in various organisms. However, current base editors suffer from severe trade-off between editing efficiency and precision. Here, based on rationally mutated cytidine deaminase domain, we develop a new base editor, YFE-BE4max, effectively narrow the editing width to as little as approximately three nucleotides while maintaining high efficiency in rabbits. Moreover, YFE-BE4max successfully mediated the Tyr p. Q68Stop and Lmna p. G607G mutation in F0 rabbit with high efficiency and precision, which precisely recapitulates the pathological features of human OCA1 and HGPS, respectively. Collectively, YFE-BE4max system provide promising tools to perform efficient base editing with high precision in rabbits and enhances its capacity to precisely model human diseases.

引用

页数：11

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