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

ABSTRACT: 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. In vitro, MyomP1 conjugation significantly increased transduction efficiency in murine and human myoblasts and myotubes. In vivo, MyomP1-LNPs significantly enhanced muscle transduction when delivering DNA cargo, strongly reduced liver accumulation following intramuscular and intravenous mRNA delivery, and attenuated local immune activatio

SUBMITTER: Ji J 

PROVIDER: S-EPMC12741376 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature