Muscle satellite cell editing by LNP-CRISPR-Cas9 to resist muscle injury

Dec 18, 2025Cell reports

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

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CRISPR Gene Editing on OpenScience ↗PubMed ↗DOI ↗

Abstract

Lipid nanoparticle-mediated delivery of CRISPR technology induces exon skipping in muscle satellite cells more efficiently than adeno-associated virus vectors.

Efficient in vivo transduction of muscle satellite cells is challenging.
Lipid nanoparticle-CRISPR delivery shows improved exon skipping in Pax7-positive satellite cells compared to adeno-associated virus.
Both intramuscular and intravenous administrations were tested in a Duchenne muscular dystrophy mouse model.
Lipid nanoparticle-CRISPR editing demonstrated greater resistance to repeated muscle injuries than adeno-associated virus-CRISPR.
These findings suggest a potential non-viral platform for genome editing in skeletal muscle.

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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.