| RRC ID |
90122
|
| 著者 |
Wang J, He Q, Zeng Y, Wu Y, Wang M, Xu W, Wang Z, Zhang X.
|
| タイトル |
A series of precise and controllable base editors with split-TadA-8e.
|
| ジャーナル |
Mol Ther Nucleic Acids
|
| Abstract |
Adenine base editors (ABEs) enable efficient A-to-G base conversions in genomic DNA, serving as powerful tools for basic research and clinical disease treatment. TadA-8e with high processive and compatibility makes ABE8e to be the most widely used adenine base editor and has also facilitated the creation of more elegant base editors based on TadA-8e fusion, such as AYBE and eA&C-BEmax. However, ABE8e has more off-target events including DNA off-target and RNA off-target, which raises safety concerns for precision gene editing. Here, we split the TadA-8e of ABE8e (sABE8e) to enable controlled adenine base editing through rapamycin-induced dimerization between FRB and FKBP12. sABE8e has comparable on-target adenine editing activity to ABE8e while maintaining reduced DNA and RNA off-target effects. Harnessing this site of split TadA-8e, we have also developed controllable AYBE (sAYBE) and eA&C-BEmax (seA&C-BEmax), which both offer similar or slightly low base editing efficiency with decreased off-targets compared to AYBE or eA&C-BEmax. These precise and controllable base editing tools will advance the future application of base editors in basic research and clinical disease treatment.
|
| 巻・号 |
36(3)
|
| ページ |
102672
|
| 公開日 |
2025-9-9
|
| DOI |
10.1016/j.omtn.2025.102672
|
| PII |
S2162-2531(25)00226-4
|
| PMID |
40917891
|
| PMC |
PMC12408220
|
| リソース情報 |
| ヒト・動物細胞 |
HUDEP-2(RCB4557) |
