A novel base editor SpRY-ABE8eF148A mediates efficient A-to-G base editing with a reduced off-target effect

A novel base editor SpRY-ABE8eF148A mediates efficient A-to-G base editing with a reduced off-target effect

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 deaminas...

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Bibliographic Details
Main Authors: Guo Li, Yaxian Cheng, Yeqiu Li, Hongru Ma, Zhongji Pu, Sa Li, Yiqiang Zhao, Xingxu Huang, Yuan Yao
Format: Article
Language:English
Published: Elsevier 2023-03-01
Series:Molecular Therapy: Nucleic Acids
Subjects:
MT: RNA/DNA Editing
ABEs
SpRY-ABE8eF148A
PAMless
narrowed window
ARDPM
Online Access:http://www.sciencedirect.com/science/article/pii/S2162253122003183
Description
Summary: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-ABE8eF148A, 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-ABE8eF148A significantly decreased the RNA off-target effect. Therefore, this engineered base editor, SpRY-ABE8eF148A, 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.
ISSN:2162-2531

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