State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, People's Republic of China.
Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, People's Republic of China.
Nat Chem Biol. 2024 Mar;20(3):277-290. doi: 10.1038/s41589-023-01531-y. Epub 2024 Feb 28.
Clustered regularly interspaced short palindromic repeats (CRISPR)-based genome editors are powerful tools in biology and hold great promise for the treatment of human diseases. Advanced DNA base editing tools, such as cytosine base editor and adenine base editor, have been developed to correct permanent mistakes in genetic material. However, undesired off-target edits would also be permanent, which poses a considerable risk for therapeutics. Alternatively, base editing at the RNA level is capable of correcting disease-causing mutations but does not lead to lasting genotoxic effects. RNA base editors offer temporary and reversible therapies and have been catching on in recent years. Here, we summarize some emerging RNA editors based on A-to-inosine, C-to-U and U-to-pseudouridine changes. We review the programmable RNA-targeting systems as well as modification enzyme-based effector proteins and highlight recent technological breakthroughs. Finally, we compare editing tools, discuss limitations and opportunities, and provide insights for the future directions of RNA base editing.
基于成簇规律间隔短回文重复序列（CRISPR）的基因组编辑技术是生物学领域的强大工具，在人类疾病治疗方面具有广阔的应用前景。先进的 DNA 碱基编辑工具，如胞嘧啶碱基编辑器和腺嘌呤碱基编辑器，已经被开发出来，以纠正遗传物质中的永久性错误。然而，非预期的脱靶编辑也将是永久性的，这给治疗带来了相当大的风险。相比之下，在 RNA 水平上进行碱基编辑能够纠正致病突变，但不会导致持久的遗传毒性效应。RNA 碱基编辑器提供了临时和可逆的治疗方法，近年来越来越受到关注。在这里，我们总结了一些基于 A 到肌苷、C 到 U 和 U 到假尿嘧啶变化的新兴 RNA 编辑器。我们回顾了可编程 RNA 靶向系统以及基于修饰酶的效应蛋白，并强调了最近的技术突破。最后，我们比较了编辑工具，讨论了局限性和机遇，并为 RNA 碱基编辑的未来方向提供了见解。
