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Although base editing has potential as a gene therapy tool, bystander edits limit its clinical use for many pathogenic mutations. This work uses directed evolution to optimize adenine base editors and 3′-extended guide RNAs to enhance targeting, producing more precise editors with reduced bystander effects.
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References
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Healey, N. Next-generation CRISPR-based gene-editing therapies tested in clinical trials. Nat. Med. 30, 2380–2381 (2023). A news article that describes current CRISPR-based gene editing clinical trials.
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Musunuru, K. et al. Patient-specific in vivo gene editing to treat a rare genetic disease. N. Engl. J. Med. 392, 2235–2243 (2025). This paper reports the first personalized base editing therapy.
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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 describes different base editing systems.
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Urnov, F. D. Imagine CRISPR cures. Mol. Ther. 29, 3103–3106 (2021). This review discusses the need for the faster development of personalized gene therapy.
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Gaudelli, N. M. et al. Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature 551, 464–471 (2017). This paper presents the development of the ABE technology.
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This is a summary of: Perrotta, R. M. et al. Engineered base editors with reduced bystander editing through directed evolution. Nat. Biotechnol. https://doi.org/10.1038/s41587-025-02937-w (2025).
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Improving adenine base editor precision with directed evolution and extended guide RNAs. Nat Biotechnol (2026). https://doi.org/10.1038/s41587-025-02977-2
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DOI: https://doi.org/10.1038/s41587-025-02977-2
