Research BriefingPublished: 02 January 2026Nature Biotechnology (2026)Cite this articleSubjectsSynthetic biologyTargeted gene repairAlthough 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.This is a preview of subscription content, access via your institutionAccess optionsAccess Nature and 54 other Nature Portfolio journalsGet Nature+, our best-value online-access subscription27,99 € / 30 dayscancel any timeLearn moreSubscribe to this journalReceive 12 print issues and online access269,00 € per yearonly 22,42 € per issueLearn moreBuy this articlePurchase on SpringerLinkInstant access to the full article PDF.39,95 €Prices may be subject to local taxes which are calculated during checkoutFig. 1: Enhancing base editing precision via directed evolution.ReferencesHealey, 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.Article Google Scholar 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.Article CAS PubMed Google Scholar 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.Article CAS PubMed PubMed Central Google Scholar 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.Article CAS PubMed PubMed Central Google Scholar 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.Article CAS PubMed PubMed Central Google Scholar Download referencesAdditional informationPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.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).Rights and permissionsReprints and permissionsAbout this article