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Engineering Miniature IscB Nickase for Robust Base Editing with Broad Targeting Range
2024
发表期刊NATURE CHEMICAL BIOLOGY (IF:12.9[JCR-2023],14.7[5-Year])
ISSN1552-4450
EISSN1552-4469
发表状态已发表
DOI10.1038/s41589-024-01670-w
摘要

["IscB has a similar domain organization to Cas9, but the small size of IscB is better suited for delivery by adeno-associated virus. To improve the low editing efficiency of OgeuIscB (IscB from human gut metagenome) in mammalian cells, we developed high-efficiency miniature base editors by engineering OgeuIscB nickase and its cognate omega RNA, termed IminiBEs. We demonstrated the robust editing efficiency of IminiCBE (67% on average) or IminiABE (52% on average). Fusing non-specific DNA-binding protein Sso7d to IminiBEs increased the editing efficiency of low-efficiency sites by around two- to threefold, and we termed it SIminiBEs. In addition, IminiCBE and SIminiCBE recognize NNRR, NNRY and NNYR target-adjacent motifs, which broaden the canonical NWRRNA target-adjacent motif sites for the wild-type IscB nickase. Overall, IminiBEs and SIminiBEs are efficient miniature base editors for site-specific genomic mutations.","By engineering a tiny OgeuIscB-omega RNA system and tethering DNA-binding protein Sso7d, the authors developed robust miniature base editors SIminiBEs, which achieved robust C-to-T and A-to-G base transitions with a broad targeting range."]

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收录类别SCI
语种英语
资助项目Shanghai Science and Technology Development Foundation (Shanghai Science and Technology Development Fund)[31970591] ; Shanghai Institute for Advanced Immunochemical Studies (SIAIS) at ShanghaiTech University - National Natural Science Foundation of China[21JC1404800]
WOS研究方向Biochemistry & Molecular Biology
WOS类目Biochemistry & Molecular Biology
WOS记录号WOS:001264685500004
出版者NATURE PORTFOLIO
引用统计
被引频次:5[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符https://kms.shanghaitech.edu.cn/handle/2MSLDSTB/370089
专题免疫化学研究所
物质科学与技术学院
生命科学与技术学院_硕士生
生命科学与技术学院_博士生
生命科学与技术学院_PI研究组_马涵慧组
免疫化学研究所_PI研究组_白芳组
生命科学与技术学院_PI研究组_孙亚东组
共同第一作者Hu, Yueer; Mo, Qiqin
通讯作者Ma, Hanhui
作者单位
1.ShanghaiTech Univ, Gene Editing Ctr, Sch Life Sci & Technol, Shanghai, Peoples R China
2.ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai, Peoples R China
3.ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China
4.Hunan Normal Univ, Sch Med, Key Lab Model Anim & Stem Cell Biol Hunan Prov, Changsha, Peoples R China
第一作者单位生命科学与技术学院
通讯作者单位生命科学与技术学院
第一作者的第一单位生命科学与技术学院
推荐引用方式
GB/T 7714
Han, Linxiao,Hu, Yueer,Mo, Qiqin,et al. Engineering Miniature IscB Nickase for Robust Base Editing with Broad Targeting Range[J]. NATURE CHEMICAL BIOLOGY,2024.
APA Han, Linxiao.,Hu, Yueer.,Mo, Qiqin.,Yang, Hao.,Gu, Feng.,...&Ma, Hanhui.(2024).Engineering Miniature IscB Nickase for Robust Base Editing with Broad Targeting Range.NATURE CHEMICAL BIOLOGY.
MLA Han, Linxiao,et al."Engineering Miniature IscB Nickase for Robust Base Editing with Broad Targeting Range".NATURE CHEMICAL BIOLOGY (2024).
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