{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Tasfaout H"],"funding":["Wellstone Center at the University of Washington","University of Washington Center for Translational Muscle Research","Diabetes Research Center","Association Française contre les Myopathies","US Department of Defense","National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health","Muscular Dystrophy Association"],"pagination":["e189075"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12321383"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["135(15)"],"pubmed_abstract":["Gene replacement therapies mediated by adeno-associated viral (AAV) vectors represent a promising approach for treating genetic diseases. However, their modest packaging capacity (~4.7 kb) remains an important constraint and significantly limits their application for genetic disorders involving large genes. A prominent example is Duchenne muscular dystrophy (DMD), whose protein product dystrophin is generated from a 11.2 kb segment of the DMD mRNA. Here, we explored methods that enable efficient expression of full-length dystrophin via triple AAV codelivery. This method exploits the protein trans-splicing mechanism mediated by split inteins. We identified a combination of efficient and specific split intein pairs that enabled the reconstitution of full-length dystrophin from 3 dystrophin f"],"journal":["The Journal of clinical investigation"],"pubmed_title":["Expression of full-length dystrophin reverses muscular dystrophy defects in young and old mdx4cv mice."],"pmcid":["PMC12321383"],"funding_grant_id":["P30AR074990","R01HL128368","P30 DK017047","P50 AR065139","1060372","24777","MD220097"],"pubmed_authors":["Tasfaout H","Tian R","Regnier M","McMillen TS","Chamberlain JS","Halbert CL","Reyes TR"],"additional_accession":[]},"is_claimable":false,"name":"Expression of full-length dystrophin reverses muscular dystrophy defects in young and old mdx4cv mice.","description":"Gene replacement therapies mediated by adeno-associated viral (AAV) vectors represent a promising approach for treating genetic diseases. However, their modest packaging capacity (~4.7 kb) remains an important constraint and significantly limits their application for genetic disorders involving large genes. A prominent example is Duchenne muscular dystrophy (DMD), whose protein product dystrophin is generated from a 11.2 kb segment of the DMD mRNA. Here, we explored methods that enable efficient expression of full-length dystrophin via triple AAV codelivery. This method exploits the protein trans-splicing mechanism mediated by split inteins. We identified a combination of efficient and specific split intein pairs that enabled the reconstitution of full-length dystrophin from 3 dystrophin f","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-03-31T11:30:53.763Z","creation":"2025-08-31T03:08:28.761Z"},"accession":"S-EPMC12321383","cross_references":{"pubmed":["40493400"],"doi":["10.1172/JCI189075"]}}