Efficient glycosylase-mediated base editing with minimal off-target effects in mammalian embryos

Developing glycosylase-based base editors (gBEs) to broaden the editing scope is highly desirable for biomedical research and agricultural applications. However, the off-target effects and applicability of gBEs need further investigation. We employ GOTI to detect rare DNA off-target events in mouse embryos injected with N-methylpurine glycosylase-based AYBE and gGBE. Transcriptome-wide RNA analysis reveals that TadA8e-V106W, derived from AYBE, induces low-frequency RNA off-target editing. Both base editors efficiently induce A/G-to-Y editing in mouse and sheep embryos, and in newborn lambs. The robust efficiency and specificity of AYBE and gGBE underscore their potential for clinical applications and genetic improvement in livestock.

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Publication Details

Journal
Genome biology
Published
2025-10-21
DOI
https://doi.org/10.1186/s13059-025-03838-6
Primary Topic
CRISPR and Genetic Engineering
Type
article
Field-Weighted Citation Impact
0.00

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article

Efficient glycosylase-mediated base editing with minimal off-target effects in mammalian embryos

Zhuo Liu, Yinghui Wei, Shuhong Huang, Xuetao Cao et al.
Genome biology
CRISPR and Genetic Engineering
article

Efficient glycosylase-mediated base editing with minimal off-target effects in mammalian embryos

Zhuo Liu, Yinghui Wei, Shuhong Huang, Xuetao Cao, Weiwei Wu, Yulin Chen, Bo Liu, Xiaolong Wang, Liqin Wang, Jiapeng Lin, Muhua Luo, Kun Xu, Wenxin Zheng, Yue Yang, Qijing Zhang, Yangsheng Wu
article en

Abstract

Developing glycosylase-based base editors (gBEs) to broaden the editing scope is highly desirable for biomedical research and agricultural applications. However, the off-target effects and applicability of gBEs need further investigation. We employ GOTI to detect rare DNA off-target events in mouse embryos injected with N-methylpurine glycosylase-based AYBE and gGBE. Transcriptome-wide RNA analysis reveals that TadA8e-V106W, derived from AYBE, induces low-frequency RNA off-target editing. Both base editors efficiently induce A/G-to-Y editing in mouse and sheep embryos, and in newborn lambs. The robust efficiency and specificity of AYBE and gGBE underscore their potential for clinical applications and genetic improvement in livestock.

Genome biologyVol. 26(1)
Hainan University (CN), North West Agriculture and Forestry University (CN), Xinjiang Academy of Animal Science (CN), Sanya University (CN), Ministry of Agriculture (TN)
National Natural Science Foundation of China, Northwest A and F University, China Agricultural Research System
Openalex Percentile: Top 73%
CRISPR and Genetic Engineering
DOIOpen Access PDFOpenAlex
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