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Programmable RNA base editing via targeted modifications

Nature Chemical Biology volume 20, pages 277–290 (2024)Cite this article

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Abstract

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.

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Fig. 1: RNA-targeting platforms and effectors.
Fig. 2: Exogenous deaminase-mediated RNA base editors.
Fig. 3: Endogenous ADAR-based RNA A-to-I base editors.
Fig. 4: Programmable RNA pseudouridylation.
Fig. 5: Genetic variants associated with disease.

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Acknowledgements

This work was supported by the National Key Research and Development Program (grant no. 2019YFA0802201 to C.Y.), the National Natural Science Foundation of China (grant nos. 92153303 and 21825701 to C.Y.), the Ministry of Agriculture and Rural Affairs of China (grant no. NK2022010102 to C.Y.) and funding from the Beijing Municipal Science & Technology Commission (grant no. Z231100002723005 to C.Y.).

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  1. These authors contributed equally: Jinghui Song, Yuan Zhuang.

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  1. State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing, People’s Republic of China

    Jinghui Song, Yuan Zhuang & Chengqi Yi

  2. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, People’s Republic of China

    Chengqi Yi

  3. Department of Chemical Biology and Synthetic and Functional Biomolecules Center, College of Chemistry and Molecular Engineering, Peking University, Beijing, People’s Republic of China

    Chengqi Yi

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Song, J., Zhuang, Y. & Yi, C. Programmable RNA base editing via targeted modifications. Nat Chem Biol 20, 277–290 (2024). https://doi.org/10.1038/s41589-023-01531-y

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