首页|A-to-G/C/T and C-to-T/G/A dual-function base editor for creating multi-nucleotide variants

A-to-G/C/T and C-to-T/G/A dual-function base editor for creating multi-nucleotide variants

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Multi-nucleotide variants(MNVs)are critical genetic variants associated with various genetic diseases.However,tools for precisely installing MNVs are limited.In this study,we present the development of a dual-base editor,BDBE,by integrating TadA-dual and engineered human N-methylpurine DNA glycosylase(eMPG)into nCas9(D10A).Our results demonstrate that BDBE effectively converts A-to-G/C/T(referred to as A-to-B)and C-to-T/G/A(referred to as C-to-D)simultaneously,yielding nine types of dinucleotides from adjacent CA nucleotides while maintaining minimal off-target effects.Notably,BDBE4 exhibits exceptional performance across multiple human cell lines and successfully simulated all nine dinucleotide MNVs from the gnomAD database.These findings indicate that BDBE significantly expands the product range of base editors and offers a valuable resource for advancing MNV research.

CRISPRGene editingDual-base editorA-to-G/C/T and C-to-T/G/AMNVGenetic diseases

Bingxiu Ma、Han Wu、Shixue Gou、Meng Lian、Cong Xia、Kaiming Yang、Long Jin、Junyuan Liu、Yunlin Wu、Yahai Shu、Haizhao Yan、Zhanjun Li、Liangxue Lai、Yong Fan

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Department of Obstetrics and Gynecology,Guangdong Provincial Key Laboratory of Major Obstetric Diseases,Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology,Guangdong-Hong Kong-Macao Greater Bay Area Higher Education Joint Laboratory of Maternal-Fetal Medicine,The Third Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong 510150,China

China-New Zealand Joint Laboratory on Biomedicine and Health,CAS Key Laboratory of Regenerative Biology,Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou,Guangdong 510530,China

Sanya Institute of Swine Resource,Hainan Provincial Research Centre of Laboratory Animals,Sanya,Hainan 572000,China

Research Unit of Generation of Large Animal Disease Models,Chinese Academy of Medical Sciences(2019RU015),Gua

Guangzhou National Laboratory,Guangzhou,Guangdong 510005,China

Institute of Laboratory Animal Sciences,Chinese Academy of Medical Sciences & Peking Union Medical College,Beijing 100020,China

Key Laboratory of Zoonosis Research,Ministry of Education,College of Animal Science,Jilin University,Changchun,Jilin 130062,China

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2024

10.1016/j.jgg.2024.10.001

遗传学报
中国遗传学会 中国科学院遗传与发育生物学研究所

遗传学报

CSTPCD
影响因子：0.821
ISSN：1673-8527
年,卷(期)：2024.51(12)