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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| Main Authors: | , , , , , , , , |
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Elsevier,
2023-03-01T00:00:00Z.
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| LEADER | 00000 am a22000003u 4500 | ||
|---|---|---|---|
| 001 | doaj_5879331a0e724251aa83eeba6bdec632 | ||
| 042 | |a dc | ||
| 100 | 1 | 0 | |a Guo Li |e author |
| 700 | 1 | 0 | |a Yaxian Cheng |e author |
| 700 | 1 | 0 | |a Yeqiu Li |e author |
| 700 | 1 | 0 | |a Hongru Ma |e author |
| 700 | 1 | 0 | |a Zhongji Pu |e author |
| 700 | 1 | 0 | |a Sa Li |e author |
| 700 | 1 | 0 | |a Yiqiang Zhao |e author |
| 700 | 1 | 0 | |a Xingxu Huang |e author |
| 700 | 1 | 0 | |a Yuan Yao |e author |
| 245 | 0 | 0 | |a A novel base editor SpRY-ABE8eF148A mediates efficient A-to-G base editing with a reduced off-target effect |
| 260 | |b Elsevier, |c 2023-03-01T00:00:00Z. | ||
| 500 | |a 2162-2531 | ||
| 500 | |a 10.1016/j.omtn.2022.12.001 | ||
| 520 | |a 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. | ||
| 546 | |a EN | ||
| 690 | |a MT: RNA/DNA Editing | ||
| 690 | |a ABEs | ||
| 690 | |a SpRY-ABE8eF148A | ||
| 690 | |a PAMless | ||
| 690 | |a narrowed window | ||
| 690 | |a ARDPM | ||
| 690 | |a Therapeutics. Pharmacology | ||
| 690 | |a RM1-950 | ||
| 655 | 7 | |a article |2 local | |
| 786 | 0 | |n Molecular Therapy: Nucleic Acids, Vol 31, Iss , Pp 78-87 (2023) | |
| 787 | 0 | |n http://www.sciencedirect.com/science/article/pii/S2162253122003183 | |
| 787 | 0 | |n https://doaj.org/toc/2162-2531 | |
| 856 | 4 | 1 | |u https://doaj.org/article/5879331a0e724251aa83eeba6bdec632 |z Connect to this object online. |