{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["16(1)"],"submitter":["Byrne SM"],"pubmed_abstract":["Custom RNA base editing exploiting the human Adenosine Deaminase Acting on RNA (ADAR) enzyme may enable therapeutic gene editing without DNA damage or use of foreign proteins. ADAR's adenosine-to-inosine (effectively A-to-G) deamination activity can be targeted to transcripts using an antisense guide RNA (gRNA), but efficacy is challenged by limits of in vivo delivery. Embedding gRNAs into a U7 small nuclear RNA (snRNA) framework greatly enhances RNA editing with endogenous ADAR, and a 750-plex single-cell mutagenesis screen further improved the framework. An optimized scaffold with a stronger synthetic U7 promoter enables 76% RNA editing in vitro from a single DNA construct per cell, and 75% editing in a Hurler syndrome mouse brain after one systemic AAV injection, surpassing circular gRNA approaches. The technology also improves published DMD exon-skipping designs 25-fold in differentiated myoblasts. Our engineered U7 framework represents a universal scaffold for ADAR-based RNA editing and other antisense RNA therapies."],"journal":["Nature communications"],"pagination":["4860"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12106830"],"repository":["biostudies-literature"],"pubmed_title":["An engineered U7 small nuclear RNA scaffold greatly increases ADAR-mediated programmable RNA base editing."],"pmcid":["PMC12106830"],"pubmed_authors":["Jiang Y","Briggs AW","Pabon R","Burleigh SM","Fragoza R","Rainaldi J","Portell A","Byrne SM","Savva Y","Kania E","Mali P"],"additional_accession":[]},"is_claimable":false,"name":"An engineered U7 small nuclear RNA scaffold greatly increases ADAR-mediated programmable RNA base editing.","description":"Custom RNA base editing exploiting the human Adenosine Deaminase Acting on RNA (ADAR) enzyme may enable therapeutic gene editing without DNA damage or use of foreign proteins. ADAR's adenosine-to-inosine (effectively A-to-G) deamination activity can be targeted to transcripts using an antisense guide RNA (gRNA), but efficacy is challenged by limits of in vivo delivery. Embedding gRNAs into a U7 small nuclear RNA (snRNA) framework greatly enhances RNA editing with endogenous ADAR, and a 750-plex single-cell mutagenesis screen further improved the framework. An optimized scaffold with a stronger synthetic U7 promoter enables 76% RNA editing in vitro from a single DNA construct per cell, and 75% editing in a Hurler syndrome mouse brain after one systemic AAV injection, surpassing circular gRNA approaches. The technology also improves published DMD exon-skipping designs 25-fold in differentiated myoblasts. Our engineered U7 framework represents a universal scaffold for ADAR-based RNA editing and other antisense RNA therapies.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 May","modification":"2026-06-02T22:32:30.51Z","creation":"2026-05-28T03:05:33.391Z"},"accession":"S-EPMC12106830","cross_references":{"pubmed":["40419487"],"doi":["10.1038/s41467-025-60155-z"]}}