Improving the precision of gene correction through RNA base editing typically involves a trade-off with efficiency. We find using G•U wobble base pairs is a universally applicable strategy to improve editing precision and efficiency, and is effective in a mouse model of Rett syndrome in vivo.
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References
Pfeiffer, L. S. & Stafforst, T. Precision RNA base editing with engineered and endogenous effectors. Nat. Biotechnol. 41, 1526–1542 (2023). This review summarizes recent RNA base editing strategies and how they tackle challenges with editing efficiency and precision.
Xu, D. et al. The electrostatic characteristics of G.U wobble base pairs. Nuc. Acids Res. 35, 3836–3847 (2007). This paper reports the structural and electrostatic effects of G•U wobble base pairs in RNA helices.
Reautschnig, P. et al. CLUSTER guide RNAs enable precise and efficient RNA editing with endogenous ADAR enzymes in vivo. Nat. Biotechnol. 40, 759–768 (2022). This paper reports the engineering of CLUSTER gRNAs that recruit endogenous ADAR.
Qu, L. et al. Programmable RNA editing by recruiting endogenous ADAR using engineered RNAs. Nat. Biotechnol. 37, 1059–1069 (2019). This paper reports the engineering of LEAPER gRNAs that recruit endogenous ADAR.
Sinnamon, J. R. et al. Targeted RNA editing in brainstem alleviates respiratory dysfunction in a mouse model of Rett syndrome. Proc. Natl Acad. Sci. USA 119, e2206053119 (2022). This paper reports the restoration of a Rett syndrome-causing mutation in Mecp2 by an exogenous ADAR approach.
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This is a summary of: Reautschnig, P. et al. Precise in vivo RNA base editing with a wobble-enhanced circular CLUSTER guide RNA. Nat. Biotechnol. https://doi.org/10.1038/s41587-024-02313-0 (2024).
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G•U wobble base pairs improve site-directed RNA base editing. Nat Biotechnol (2024). https://doi.org/10.1038/s41587-024-02323-y
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DOI: https://doi.org/10.1038/s41587-024-02323-y