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Current therapeutic strategies, such as exon\u2010skipping and gene therapy, face limitations including truncated dystrophin production and safety concerns. To address these issues, a novel mRNA\u2010based therapy is explored using polyplex nanomicelles to deliver mRNA encoding peroxisome proliferator\u2010activated receptor gamma coactivator 1 alpha isoform 4 (PGC\u20101\u03b14) via hydrodynamic limb vein (HLV) administration. Using an in vivo muscle torque measurement technique, it is observed that nanomicelle\u2010delivered\n                    <jats:italic>Pgc\u20101\u03b14<\/jats:italic>\n                    mRNA significantly improved muscle damage resistance and mitochondrial activity in mdx mice. Specifically, HLV administration of\n                    <jats:italic>Pgc\u20101\u03b14<\/jats:italic>\n                    mRNA in dystrophic muscles significantly relieved the torque reduction and myofiber injury induced by eccentric contraction (ECC), boosted metabolic gene expression, and enhanced muscle oxidative capacity. In comparison, lipid nanoparticles (LNPs), a widely used mRNA delivery system, does not achieve similar protective effects, likely due to their intrinsic immunogenicity. This foundational proof\u2010of\u2010concept study highlights the potential of mRNA\u2010based therapeutics for the treatment of neuromuscular diseases such as DMD and demonstrates the capability of polyplex nanomicelles as a safe and efficient mRNA delivery system for therapeutic applications.\n                  <\/jats:p>","DOI":"10.1002\/advs.202409065","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T01:36:44Z","timestamp":1741743404000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Polyplex Nanomicelle\u2010Mediated\n                    <i>Pgc\u20101\u03b14<\/i>\n                    mRNA Delivery Via Hydrodynamic Limb Vein Injection Enhances Damage Resistance in Duchenne Muscular Dystrophy Mice"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3713-6246","authenticated-orcid":false,"given":"Xuan","family":"Du","sequence":"first","affiliation":[{"name":"Department of Biofunction Research Laboratory for Biomaterials and Bioengineering, Institute of Integrated Research Institute of Science Tokyo  Tokyo 101\u20100062 Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1159-3676","authenticated-orcid":false,"given":"Hideyuki","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Department of Biofunction Research Laboratory for Biomaterials and Bioengineering, Institute of Integrated Research Institute of Science Tokyo  Tokyo 101\u20100062 Japan"},{"name":"Clinical Biotechnology Team Center for Infectious Disease Education and Research (CiDER) Osaka University Osaka 565\u20100871 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