Myomerger-derived peptide enhances skeletal muscle tropism and reduces liver transduction of lipid nanoparticles for gene delivery.

Fiche publication

Date publication

mars 2026

Journal

Molecular therapy. Nucleic acids

Auteurs

Membres identifiés du Cancéropôle Est :
Mr EBERLING Pascal

Tous les auteurs :
Ji J, Lipkow E, Anton N, Crucifix C, Eberling P, Laporte J

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/41458876

Résumé

Lipid nanoparticles (LNPs) are emerging as nonviral vectors for gene therapy; yet, their strong liver tropism and lack of tissue specificity remain limiting. Here, we developed, through rational design, a skeletal muscle-targeted delivery platform by functionalizing LNPs with MyomP1, an extracellular conserved peptide derived from the muscle-specific fusogenic protein Myomerger. MyomP1-LNPs were engineered to encapsulate plasmid DNA or mRNA. , MyomP1 conjugation significantly increased transduction efficiency in murine and human myoblasts and myotubes. , MyomP1-LNPs significantly enhanced muscle transduction when delivering DNA cargo, strongly reduced liver accumulation following intramuscular and intravenous mRNA delivery, and attenuated local immune activation. This work demonstrates a ligand-guided strategy to overcome organ-specific barriers in nonviral gene transfer, with improved safety and specificity. It suggests that MyomP1-engineered LNPs hold strong potential to improve therapeutic outcomes for patients with rare muscle diseases, offering a promising alternative to traditional viral gene therapy platforms.