Generating A-to-C transversions in specific targets via base editing technology has been challenging. By fusing an evolved alkyladenine DNA glycosylase with an engineered adenine deaminase TadA-8e variant and nickase Cas9, we have developed A-to-C base editors that generate precise and efficient A-to-C transversions in cells and in mouse embryos, expanding the possible applications of base editing.
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References
Rees, H. A. & Liu, D. R. Base editing: precision chemistry on the genome and transcriptome of living cells. Nat. Rev. Genet. 19, 770–788 (2018). This review article presents advances in base editors.
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Chen, L. et al. Re-engineering the adenine deaminase TadA-8e for efficient and specific CRISPR-based cytosine base editing. Nat. Biotechnol. 41, 663–672 (2023). This paper compares cytosine conversions induced by several CGBEs and CBEs using unnatural or natural cytosine deaminases.
Chen, L. et al. Engineering a precise adenine base editor with minimal bystander editing. Nat. Chem. Biol. 19, 101–110 (2023). This paper reports the residues in adenine deaminase TadA-8e that are mutated to narrow the targeting window of this deaminase.
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This is a summary of: Chen, L. et al. Adenine transversion editors enable precise, efficient A•T-to-C•G base editing in mammalian cells and embryos. Nat. Biotechnol. https://doi.org/10.1038/s41587-023-01821-9 (2023).
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Efficient A-to-C base editing with high specificity. Nat Biotechnol 42, 578–579 (2024). https://doi.org/10.1038/s41587-023-01866-w
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DOI: https://doi.org/10.1038/s41587-023-01866-w
