biostudies-literatureDu XJapan Science and Technology AgencyJapan Agency for Medical Research and Development (AMED)e2409065https://www.ebi.ac.uk/biostudies/studies/S-EPMC12021044biostudies-literatureUnknown12(16)Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene, leading to the absence of dystrophin and progressive muscle degeneration. Current therapeutic strategies, such as exon-skipping and gene therapy, face limitations including truncated dystrophin production and safety concerns. To address these issues, a novel mRNA-based therapy is explored using polyplex nanomicelles to deliver mRNA encoding peroxisome proliferator-activated receptor gamma coactivator 1 alpha isoform 4 (PGC-1α4) via hydrodynamic limb vein (HLV) administration. Using an in vivo muscle torque measurement technique, it is observed that nanomicelle-delivered Pgc-1α4 mRNA significantly improved muscle damage resistance and mitochondrial activity in mdx mice. Specifically, HLV administration of Pgc-1α4 mRNAAdvanced science (Weinheim, Baden-Wurttemberg, Germany)Polyplex Nanomicelle-Mediated Pgc-1α4 mRNA Delivery Via Hydrodynamic Limb Vein Injection Enhances Damage Resistance in Duchenne Muscular Dystrophy Mice.PMC12021044JPMJPF2202JP223fa62700223fk0310515s050223ek0109659h000123ak0101173s0203Minegishi KSin YItaka KNakanishi HYamada TMotohashi NDu XAoki YfalsePolyplex Nanomicelle-Mediated Pgc-1α4 mRNA Delivery Via Hydrodynamic Limb Vein Injection Enhances Damage Resistance in Duchenne Muscular Dystrophy Mice.Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene, leading to the absence of dystrophin and progressive muscle degeneration. Current therapeutic strategies, such as exon-skipping and gene therapy, face limitations including truncated dystrophin production and safety concerns. To address these issues, a novel mRNA-based therapy is explored using polyplex nanomicelles to deliver mRNA encoding peroxisome proliferator-activated receptor gamma coactivator 1 alpha isoform 4 (PGC-1α4) via hydrodynamic limb vein (HLV) administration. Using an in vivo muscle torque measurement technique, it is observed that nanomicelle-delivered Pgc-1α4 mRNA significantly improved muscle damage resistance and mitochondrial activity in mdx mice. Specifically, HLV administration of Pgc-1α4 mRNA2025-01-01T00:00:00Z2025 Apr2026-07-15T08:50:46.635Z2025-07-11T03:05:54.944ZS-EPMC120210444005117810.1002/advs.202409065