biostudies-literatureEmami MRNational Institute of Allergy and Infectious DiseasesNational Institute of Arthritis and Musculoskeletal and Skin DiseasesNational Institute of Neurological Disorders and StrokeNIAID NIH HHSCystic Fibrosis FoundationPfizerCystic Fibrosis Foundation Therapeutics IncAmerican Lebanese Syrian Associated CharitiesNINDS NIH HHSNational Institutes of HealthUS Department of DefensePetroleum Technology Alliance Canada101349https://www.ebi.ac.uk/biostudies/studies/S-EPMC11546459biostudies-literatureUnknown32(4)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 interfMolecular therapy. Methods & clinical developmentSingle cell and TCR analysis of immune cells from AAV gene therapy-dosed Duchenne muscular dystrophy patients.PMC11546459P50AR052646R01NS117912R21AI169085R01NS120060R01AI136514R21 NS114918T32 AI177324R01HL061322U01AI150747R01NS047726Pellegrini MMcNally EMFarahat PKSpencer MJCasinghino SLanz TASchattgen SABrimble MAVillalta SAOwens JEspinoza AYoung CSWhiteley LOThomas PGEmami MRfalseSingle cell and TCR analysis of immune cells from AAV gene therapy-dosed Duchenne muscular dystrophy patients.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 interf2024-01-01T00:00:00Z2024 Dec2026-06-01T20:39:04.599Z2026-05-22T03:08:16.499ZS-EPMC115464593952497410.1016/j.omtm.2024.101349