Research BriefingPublished: 22 October 2026Nature Biotechnology (2026) Cite this articleView saved researchALTER is a programmable RNA base editor built entirely from human proteins. By using human AGO2 instead of bacterial CRISPR–Cas proteins, ALTER mitigates a key risk factor for harmful immune responses in therapeutic applications while also proving generally more effective than dCas13-based editors.This is a preview of subscription content, access via your institutionAccess options Access through your institutionAccess Nature and 54 other Nature Portfolio journalsGet Nature+, our best-value online-access subscription27.99 € / 30 days cancel any timeLearn moreSubscribe to this journalReceive 12 print issues and online access269.00 € per year only 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: ALTER.SubjectsNucleic-acid therapeuticsTargeted gene repairReferencesCharlesworth, C. T. et al. Identification of preexisting adaptive immunity to Cas9 proteins in humans. Nat. Med. 25, 249–254 (2019). This study identified the high prevalence of anti-Cas antibodies and T cell responses in humans.Article CAS PubMed PubMed Central Google Scholar Iwakawa, H. & Tomari, Y. Life of RISC: formation, action, and degradation of RNA-induced silencing complex. Mol. Cell 82, 30–43 (2022). A review on AGO2 function in RNAi that covers all stages of the process.Article CAS PubMed Google Scholar Becker, W. R. et al. High-throughput analysis reveals rules for target RNA binding and cleavage by AGO2. Mol. Cell 75, 741–755.e11 (2019). This study incorporated large-scale testing of how different gRNA characteristics impact AGO2 binding and target cleavage.Article CAS PubMed PubMed Central Google Scholar Huang, X. et al. Programmable C-to-U RNA editing using the human APOBEC3A deaminase. EMBO J. 39, e104741 (2020). The study describes the engineering of CURE editors.Article CAS PubMed PubMed Central Google Scholar Wolfsberg, E. et al. Machine-guided dual-objective protein engineering for deimmunization and therapeutic functions. Cell Syst. 16, 101299 (2025). An AI-assisted workflow for deimmunization of engineered protein fusions.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: Lusi, R. F. et al. Engineered human Argonaute 2 for targeted C-to-U RNA base editing. Nat. Biotechnol. https://doi.org/10.1038/s41587-026-03359-y (2026).Rights and permissionsReprints and permissionsAbout this article