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

アクセス数:575件（2025-08-21 03:03 集計）

固定URL: https://hdl.handle.net/11094/100965

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タイトル
Polyplex Nanomicelle-Mediated Pgc-1α4 mRNA Delivery Via Hydrodynamic Limb Vein Injection Enhances Damage Resistance in Duchenne Muscular Dystrophy Mice
著者
著者名
Du, Xuan
著者名
Nakanishi, Hideyuki
著者名
Yamada, Takashi
著者名
Sin, Yooksil
NRID
1000060568814 1000060568814
著者名
Minegishi, Katsura
NRID
1000050532727 1000050532727
著者名
Motohashi, Norio
NRID
1000080534172 1000080534172
著者名
Aoki, Yoshitsugu
NRID
1000060292926 1000060292926
researchmap permalink
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著者名
Itaka, Keiji
キーワード等
duchenne muscular dystrophy (DMD)
lipid nanoparticle (LNP)
mRNA therapeutics
peroxisome proliferator-activated receptor gamma coactivator (PGC-1α)
polyplex nanomicelle
内容
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.
抄録
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.
出版者
John Wiley and Sons Inc
収録物名
Advanced Science
ページ
2409065
刊行年月
2025-03-06
言語
英語
ハンドルURL
https://hdl.handle.net/11094/100965
eISSN
21983844
関連情報 (isIdenticalTo)
DOI (出版社版)
https://doi.org/10.1002/advs.202409065
アクセス権
open access
権利情報
This article is licensed under a Creative Commons Attribution 4.0 International License.
出版タイプ
Version of Record
カテゴリ
学術雑誌論文 Journal Article