{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Emami MR"],"funding":["National Institute of Allergy and Infectious Diseases","National Institute of Arthritis and Musculoskeletal and Skin Diseases","National Institute of Neurological Disorders and Stroke","NIAID NIH HHS","Cystic Fibrosis Foundation","Pfizer","Cystic Fibrosis Foundation Therapeutics Inc","American Lebanese Syrian Associated Charities","NINDS NIH HHS","National Institutes of Health","US Department of Defense","Petroleum Technology Alliance Canada"],"pagination":["101349"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11546459"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["32(4)"],"pubmed_abstract":["Clinical trials for Duchenne muscular dystrophy (DMD) are assessing the therapeutic efficacy of systemically delivered adeno-associated virus (AAV) carrying a modified <i>DMD</i> transgene. High vector doses (>1E14 vg/kg) are needed to globally transduce skeletal muscles; however, such doses trigger immune-related adverse events. Mitigating these immune responses is crucial for widespread application of AAV-based therapies. We used single-cell RNA sequencing and T cell receptor (TCR) sequencing on peripheral blood mononuclear cells from five participants prior to, and after, dosing. One subject in the high-dose cohort experienced thrombotic microangiopathy (TMA). Few changes in cell frequencies occurred after treatment; however, differential gene expression demonstrated induction of interf"],"journal":["Molecular therapy. Methods & clinical development"],"pubmed_title":["Single cell and TCR analysis of immune cells from AAV gene therapy-dosed Duchenne muscular dystrophy patients."],"pmcid":["PMC11546459"],"funding_grant_id":["P50AR052646","R01NS117912","R21AI169085","R01NS120060","R01AI136514","R21 NS114918","T32 AI177324","R01HL061322","U01AI150747","R01NS047726"],"pubmed_authors":["Pellegrini M","McNally EM","Farahat PK","Spencer MJ","Casinghino S","Lanz TA","Schattgen SA","Brimble MA","Villalta SA","Owens J","Espinoza A","Young CS","Whiteley LO","Thomas PG","Emami MR"],"additional_accession":[]},"is_claimable":false,"name":"Single cell and TCR analysis of immune cells from AAV gene therapy-dosed Duchenne muscular dystrophy patients.","description":"Clinical trials for Duchenne muscular dystrophy (DMD) are assessing the therapeutic efficacy of systemically delivered adeno-associated virus (AAV) carrying a modified <i>DMD</i> transgene. High vector doses (>1E14 vg/kg) are needed to globally transduce skeletal muscles; however, such doses trigger immune-related adverse events. Mitigating these immune responses is crucial for widespread application of AAV-based therapies. We used single-cell RNA sequencing and T cell receptor (TCR) sequencing on peripheral blood mononuclear cells from five participants prior to, and after, dosing. One subject in the high-dose cohort experienced thrombotic microangiopathy (TMA). Few changes in cell frequencies occurred after treatment; however, differential gene expression demonstrated induction of interf","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Dec","modification":"2026-06-01T20:39:04.599Z","creation":"2026-05-22T03:08:16.499Z"},"accession":"S-EPMC11546459","cross_references":{"pubmed":["39524974"],"doi":["10.1016/j.omtm.2024.101349"]}}