CABE-RY: A PAM-flexible dual-mutation base editor for reliable modeling of multi-nucleotide variants

Wanyu Tao; Qing Liu; Shisheng Huang; Xin Wang; Shiyuan Qu; Junfan Guo; Danfeng Ou; Guanglei Li; Yu Zhang; Xiangmin Xu; Xingxu Huang

Molecular Therapy: Nucleic Acids (Dec 2021)

CABE-RY: A PAM-flexible dual-mutation base editor for reliable modeling of multi-nucleotide variants

Wanyu Tao,
Qing Liu,
Shisheng Huang,
Xin Wang,
Shiyuan Qu,
Junfan Guo,
Danfeng Ou,
Guanglei Li,
Yu Zhang,
Xiangmin Xu,
Xingxu Huang

Affiliations

Wanyu Tao: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China
Qing Liu: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China
Shisheng Huang: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China
Xin Wang: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China
Shiyuan Qu: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China
Junfan Guo: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China
Danfeng Ou: International Academy of Optoelectronics at Zhaoqing, South China Normal University, Zhaoqing 526238, China
Guanglei Li: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China
Yu Zhang: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China
Xiangmin Xu: Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China; Guangdong Genetic Testing Engineering Research Center, Guangzhou, Guangdong 510515, China; Corresponding author: Xiangmin Xu, Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, China.
Xingxu Huang: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding author: Xingxu Huang, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.

Journal volume & issue: Vol. 26
pp. 114 – 121

Abstract

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Multi-nucleotide variants (MNVs) represent an important type of genetic variation and have biological and clinical significance. To simulate MNVs, we designed four dual-mutation base editors combining hA3A(Y130F), TadA8e(V106W), and protospacer adjacent motif (PAM)-flexible SpRY and selected cytosine and adenine base editor-SpRY (CABE-RY), which had the best editing performance, for further study. Characterization and comparison showed that CABE-RY had a smaller DNA editing window and lower RNA off-target edits than the corresponding single base editors. Thus, we have established a versatile tool to efficiently simulate MNVs over the genome, which could be very useful for functional studies on MNVs in humans.

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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