Molecular therapy. Nucleic acidsDec 29, 2025

Peptide from Myomerger improves muscle targeting and lowers liver delivery of lipid nanoparticles for gene therapy

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

MyomP1-functionalized lipid nanoparticles may steer gene delivery toward skeletal muscle and away from liver in preclinical systems.

Evidence

This formulation/platform study tested MyomP1-LNPs with plasmid DNA or mRNA in murine and human muscle cells and in in vivo delivery experiments.

Caveat

The abstract reports delivery, biodistribution, and local immune-activation endpoints rather than therapeutic efficacy in rare muscle disease patients.

Simplified

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. In vitro In vivo