Optimizing linker length of base editors for precise crop breeding and gene therapy

Yuanyuan Shi; Yuxin Yuan; Lang Qin; Fangfang Zhou; Guochuan Wu; Baitao Li; Pengcheng Yao; Mingyan Shi; Linsha Ma; Yi Wang; Yuan Zhang; Chen Wang; Xuanye Wang; Bei Huang; Jie Chen; Zhiming Xiang; Qiupeng Lin; Jiaying Huang

doi:10.1016/j.jgg.2026.02.021

文章导航 > Journal of Genetics and Genomics > 2026 > 优先出版

Yuanyuan Shi, Yuxin Yuan, Lang Qin, Fangfang Zhou, Guochuan Wu, Baitao Li, Pengcheng Yao, Mingyan Shi, Linsha Ma, Yi Wang, Yuan Zhang, Chen Wang, Xuanye Wang, Bei Huang, Jie Chen, Zhiming Xiang, Qiupeng Lin, Jiaying Huang. Optimizing linker length of base editors for precise crop breeding and gene therapy[J]. 遗传学报. doi: 10.1016/j.jgg.2026.02.021

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Optimizing linker length of base editors for precise crop breeding and gene therapy

doi: 10.1016/j.jgg.2026.02.021

Yuanyuan Shi^a,
Yuxin Yuan^b,c,d,
Lang Qin^b,c,d,e,
Fangfang Zhou^a,
Guochuan Wu^a,
Baitao Li^b,c,d,
Pengcheng Yao^a,
Mingyan Shi^b,c,d,
Linsha Ma^b,c,d,
Yi Wang^b,c,d,
Yuan Zhang^b,c,d,
Chen Wang^a,
Xuanye Wang^a,
Bei Huang^a,
Jie Chen^a,
Zhiming Xiang^a,
Qiupeng Lin^b,c,d,f, ,,
Jiaying Huang^a, ,

a. Department of Radiology, The Affiliated Panyu Central Hospital, GMU-GIBH Joint School of Life Sciences, Guangdong Provincial Key Laboratory of Protein Modification and Disease, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Medical University, Guangzhou, Guangdong 511436, China;
b. Guangdong Basic Research Center of Excellence for Precise Breeding of Future Crops, College of Agriculture, South China Agricultural University, Guangzhou, Guangdong 510642, China;
c. State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangdong Provincial Key Laboratory of Plant Molecular Breeding, South China Agricultural University, Guangzhou, Guangdong 510642, China;
d. Key Laboratory for Enhancing Resource Use Efficiency of Crops in South China, Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou, Guangdong 510642, China;
e. College of Fisheries, Southwest University, Chongqing 402460, China;
f. Institute of BioFoundry, College of Life Sciences, South China Agricultural University, Guangzhou, Guangdong 510642, China

基金项目:

Thanks for the instrument analysis and measurement provided by the Scientific Research Center of Guangzhou Medical University and Center of Genomics and Bioinformatics of South China Agricultural University. We thank Kewei Xu for his insightful comments on the manuscript. Parts of the figures were created with BioRender.

详细信息

通讯作者:
Qiupeng Lin,E-mail:qiupenglin@scau.edu.cn

Jiaying Huang,E-mail:huangjy@gzhmu.edu.cn

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出版历程
- 收稿日期: 2025-10-30
- 录用日期: 2026-02-24
- 修回日期: 2026-02-14
- 网络出版日期: 2026-02-28

Optimizing linker length of base editors for precise crop breeding and gene therapy

Yuanyuan Shi^a,
Yuxin Yuan^b,c,d,
Lang Qin^b,c,d,e,
Fangfang Zhou^a,
Guochuan Wu^a,
Baitao Li^b,c,d,
Pengcheng Yao^a,
Mingyan Shi^b,c,d,
Linsha Ma^b,c,d,
Yi Wang^b,c,d,
Yuan Zhang^b,c,d,
Chen Wang^a,
Xuanye Wang^a,
Bei Huang^a,
Jie Chen^a,
Zhiming Xiang^a,
Qiupeng Lin^{b,c,d,f
, ,},
Jiaying Huang^{a
, ,}

a. Department of Radiology, The Affiliated Panyu Central Hospital, GMU-GIBH Joint School of Life Sciences, Guangdong Provincial Key Laboratory of Protein Modification and Disease, The Guangdong-Hong Kong-Macao Joint Laboratory for Cell Fate Regulation and Diseases, Guangzhou Medical University, Guangzhou, Guangdong 511436, China;
b. Guangdong Basic Research Center of Excellence for Precise Breeding of Future Crops, College of Agriculture, South China Agricultural University, Guangzhou, Guangdong 510642, China;
c. State Key Laboratory for Conservation and Utilization of Subtropical Agro-Bioresources, Guangdong Provincial Key Laboratory of Plant Molecular Breeding, South China Agricultural University, Guangzhou, Guangdong 510642, China;
d. Key Laboratory for Enhancing Resource Use Efficiency of Crops in South China, Ministry of Agriculture and Rural Affairs, South China Agricultural University, Guangzhou, Guangdong 510642, China;
e. College of Fisheries, Southwest University, Chongqing 402460, China;
f. Institute of BioFoundry, College of Life Sciences, South China Agricultural University, Guangzhou, Guangdong 510642, China

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摘要

摘要: Base editing enables efficient nucleotide conversions without inducing DNA double-strand breaks (DSBs) or requiring exogenous donor DNA templates. However, its broader editing window often causes bystander editing, increasing the risk of unintended mutations. In this study, we find that linker length significantly influences the editing window, and base editors with a 7-amino-acid linker reduce bystander editing by an average of 54.4% across 13 endogenous genomic sites in both rice and human cell lines. We further develop an optimized strategy by modulating the linker length between various deaminases and Cas9 nickases, which effectively reduces bystander editing across multiple applications, including functional studies, precise crop breeding, and correction of pathogenic variants. Our work reveals that shortening the linker enhances the specificity of base editing, addressing a key safety concern for its agricultural and therapeutic applications.
- Base editing /
- Linker length /
- Editing window /
- Bystander editing /
- Precise Crop breeding /
- Therapeutic application
Abstract: Base editing enables efficient nucleotide conversions without inducing DNA double-strand breaks (DSBs) or requiring exogenous donor DNA templates. However, its broader editing window often causes bystander editing, increasing the risk of unintended mutations. In this study, we find that linker length significantly influences the editing window, and base editors with a 7-amino-acid linker reduce bystander editing by an average of 54.4% across 13 endogenous genomic sites in both rice and human cell lines. We further develop an optimized strategy by modulating the linker length between various deaminases and Cas9 nickases, which effectively reduces bystander editing across multiple applications, including functional studies, precise crop breeding, and correction of pathogenic variants. Our work reveals that shortening the linker enhances the specificity of base editing, addressing a key safety concern for its agricultural and therapeutic applications.
- Base editing /
- Linker length /
- Editing window /
- Bystander editing /
- Precise Crop breeding /
- Therapeutic application

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Optimizing linker length of base editors for precise crop breeding and gene therapy

doi: 10.1016/j.jgg.2026.02.021

通讯作者:
Qiupeng Lin,E-mail:qiupenglin@scau.edu.cn

Jiaying Huang,E-mail:huangjy@gzhmu.edu.cn

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Optimizing linker length of base editors for precise crop breeding and gene therapy

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留言板

Optimizing linker length of base editors for precise crop breeding and gene therapy

doi: 10.1016/j.jgg.2026.02.021

通讯作者: Qiupeng Lin,E-mail:qiupenglin@scau.edu.cn Jiaying Huang,E-mail:huangjy@gzhmu.edu.cn

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出版历程

Optimizing linker length of base editors for precise crop breeding and gene therapy

计量

出版历程

目录

通讯作者:
Qiupeng Lin,E-mail:qiupenglin@scau.edu.cn

Jiaying Huang,E-mail:huangjy@gzhmu.edu.cn