| Programmable RNA base editing with a single gRNA-free enzyme |
| 论文作者 |
Han, WJ; Huang, WD; Wei, T; Ye, YW; Mao, MW; Wang, ZF |
| 期刊/会议名称 |
NUCLEIC ACIDS RESEARCH |
| 论文年度 |
2022 |
| 论文类别 |
Article |
| 摘要 |
Programmable RNA editing enables rewriting gene expression without changing genome sequences. Current tools for specific RNA editing dependent on the assembly of guide RNA into an RNA/protein complex, causing delivery barrier and low editing efficiency. We report a new gRNA-free system, RNA editing with individual RNA-binding enzyme (REWIRE), to perform precise base editing with a single engineered protein. This artificial enzyme contains a human-originated programmable PUF domain to specifically recognize RNAs and different deaminase domains to achieve efficient A-to-I or C-to-U editing, which achieved 60-80% editing rate in human cells, with a few non-specific editing sites in the targeted region and a low level off-target effect globally. The RNA-binding domain in REWIREs was further optimized to improve editing efficiency and minimize off-target effects. We applied the REWIREs to correct disease-associated mutations and achieve both types of base editing in mice. As a single-component system originated from human proteins, REWIRE presents a precise and efficient RNA editing platform with broad applicability. |
| 期 |
16 |
| 卷 |
50 |
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