2025-03-25 東京科学大学
ChatGPT:
<関連情報>
- https://www.isct.ac.jp/ja/news/h3g0u465e3x0
- https://www.isct.ac.jp/plugins/cms/component_download_file.php?type=2&pageId=&contentsId=1&contentsDataId=656&prevId=&key=96838122917e3903c932ff701eb19de3.pdf
- https://advanced.onlinelibrary.wiley.com/doi/10.1002/advs.202409065
ポリプレックスナノミセルを介したPgc-1α4 mRNAの流体力学的四肢静脈注射による送達がデュシェンヌ型筋ジストロフィーマウスの損傷抵抗性を高める Polyplex Nanomicelle-Mediated Pgc-1α4 mRNA Delivery Via Hydrodynamic Limb Vein Injection Enhances Damage Resistance in Duchenne Muscular Dystrophy Mice
Xuan Du, Hideyuki Nakanishi, Takashi Yamada, Yooksil Sin, Katsura Minegishi, Norio Motohashi, Yoshitsugu Aoki, Keiji Itaka
Advanced Science Published: 06 March 2025
DOI: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.
