Cell reportsDec 18, 2025

Using gene editing with lipid particles to help muscle stem cells resist injury

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 27, 2026

Abstract

Essence

LNP-CRISPR edited muscle satellite cells in a DMD mouse model and showed greater durability after repeated muscle injury than AAV-CRISPR.

Evidence

This preclinical platform experiment compared lipid nanoparticle delivery of CRISPR-Cas9 mRNA and guide RNA with AAV vectors after intramuscular or intravenous administration in a Duchenne muscular dystrophy mouse model.

Caveat

The evidence is limited to mouse-model genome editing and injury-resistance endpoints, so safety, dosing, durability, and therapeutic benefit in people with DMD remain untested.

Simplified

Muscle satellite cells are essential for skeletal muscle regeneration and represent an attractive therapeutic target for gene delivery in Duchenne muscular dystrophy (DMD). However, efficient in vivo transduction of these cells has remained challenging. Here, we demonstrate that lipid nanoparticle (LNP)-mediated delivery of Streptococcus pyogenes CRISPR-Cas9 mRNA and guide RNA (LNP-CRISPR) induces exon skipping in Pax7-positive satellite cells more efficiently than adeno-associated virus (AAV) vectors following intramuscular or intravenous administration in a DMD mouse model. Furthermore, unlike AAV-CRISPR, LNP-CRISPR-mediated genome editing showed greater resistance to repeated muscle injuries, indicating successful editing of regenerative satellite cells. These results highlight the potential of LNPs as a non-viral platform for durable genome editing in skeletal muscle and lay the foundation for developing safe and sustainable genome-editing therapies for DMD.