Polyplex Nanomicelle-Mediated Pgc-1α4 mRNA Delivery Via Hydrodynamic Limb Vein Injection Enhances Damage Resistance in Duchenne Muscular Dystrophy Mice

Du, Xuan; Nakanishi, Hideyuki; Yamada, Takashi et al.

Advanced Science, 2025, 2409065

Number of Access:575（2025-08-21 07:02 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/100965

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Title
Polyplex Nanomicelle-Mediated Pgc-1α4 mRNA Delivery Via Hydrodynamic Limb Vein Injection Enhances Damage Resistance in Duchenne Muscular Dystrophy Mice
Creator
CreatorName
Du, Xuan
CreatorName
Nakanishi, Hideyuki
CreatorName
Yamada, Takashi
CreatorName
Sin, Yooksil
NRID
1000060568814 1000060568814
CreatorName
Minegishi, Katsura
NRID
1000050532727 1000050532727
CreatorName
Motohashi, Norio
NRID
1000080534172 1000080534172
CreatorName
Aoki, Yoshitsugu
NRID
1000060292926 1000060292926
researchmap permalink
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CreatorName
Itaka, Keiji
Subject
duchenne muscular dystrophy (DMD)
lipid nanoparticle (LNP)
mRNA therapeutics
peroxisome proliferator-activated receptor gamma coactivator (PGC-1α)
polyplex nanomicelle
Description
Du X., Nakanishi H., Yamada T., et al. Polyplex Nanomicelle-Mediated Pgc-1α4 mRNA Delivery Via Hydrodynamic Limb Vein Injection Enhances Damage Resistance in Duchenne Muscular Dystrophy Mice. Advanced Science , (2025); https://doi.org/10.1002/advs.202409065.
Abstract
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 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-of-concept study highlights the potential of mRNA-based 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.
Publisher
John Wiley and Sons Inc
Source Title
Advanced Science
Page
2409065
Date of Issued
2025-03-06
Language
English
Handle URL
https://hdl.handle.net/11094/100965
eISSN
21983844
Relation.isIdenticalTo
DOI (Publisher Version)
https://doi.org/10.1002/advs.202409065
Access Rights
open access
CopyRight
This article is licensed under a Creative Commons Attribution 4.0 International License.
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Version of Record
Category
学術雑誌論文 Journal Article