دورية أكاديمية

A novel base editor SpRY-ABE8e F148A mediates efficient A-to-G base editing with a reduced off-target effect.

التفاصيل البيبلوغرافية
العنوان: A novel base editor SpRY-ABE8e F148A mediates efficient A-to-G base editing with a reduced off-target effect.
المؤلفون: Li G; ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, Zhejiang 311200, China.; College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China., Cheng Y; ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, Zhejiang 311200, China.; College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China., Li Y; ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, Zhejiang 311200, China., Ma H; ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, Zhejiang 311200, China.; College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China., Pu Z; ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, Zhejiang 311200, China.; College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China., Li S; State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China., Zhao Y; State Key Laboratory of Agrobiotechnology, China Agricultural University, Beijing 100193, China., Huang X; Zhejiang Lab, Hangzhou, Zhejiang 311121, China.; School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, China.; CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai 200031, China., Yao Y; ZJU-Hangzhou Global Scientific and Technological Innovation Center, Zhejiang University, Hangzhou, Zhejiang 311200, China.; College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310027, China.
المصدر: Molecular therapy. Nucleic acids [Mol Ther Nucleic Acids] 2022 Dec 07; Vol. 31, pp. 78-87. Date of Electronic Publication: 2022 Dec 07 (Print Publication: 2023).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: United States NLM ID: 101581621 Publication Model: eCollection Cited Medium: Print ISSN: 2162-2531 (Print) Linking ISSN: 21622531 NLM ISO Abbreviation: Mol Ther Nucleic Acids Subsets: PubMed not MEDLINE
أسماء مطبوعة: Publication: 2017- : Cambridge, MA : Cell Press
Original Publication: New York, NY : Nature Pub. Group
مستخلص: Adenine base editors (ABEs) can mediate two transition mutations, A-to-G and T-to-C, which are suitable for repairing G·C-to-T·A pathogenic variants, the most significant human pathogenic variant. By combining the protospacer adjacent motif (PAM)less SpRY nuclease with F148A-mutated TadA∗8e deaminase, we developed a new editor, SpRY-ABE8e F148A , in this study, which has narrowed the editing range and enhanced A-to-G editing efficiency in most sites with NR/YN PAMs. Furthermore, compared with SpRY-ABE8e, SpRY-ABE8e F148A significantly decreased the RNA off-target effect. Therefore, this engineered base editor, SpRY-ABE8e F148A , expanded the editing scope and improved the editing precision for G·C-to-T·A pathogenic variants. Besides, we established a bioinformatics tool, adenine base-repairing sgRNA database of pathogenic variant (ARDPM), to facilitate the development of precise editors.
Competing Interests: The authors declare that they have no competing interests.
(© 2022 The Author(s).)
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فهرسة مساهمة: Keywords: ABEs; ARDPM; MT: RNA/DNA Editing; PAMless; SpRY-ABE8eF148A; narrowed window
تواريخ الأحداث: Date Created: 20230109 Latest Revision: 20230111
رمز التحديث: 20240829
مُعرف محوري في PubMed: PMC9804010
DOI: 10.1016/j.omtn.2022.12.001
PMID: 36618266
قاعدة البيانات: MEDLINE
الوصف
تدمد:2162-2531
DOI:10.1016/j.omtn.2022.12.001