Muscle-specific gene editing therapy via mammalian fusogen-directed virus-like particles

Oct 15, 2025Nature communications

Targeted Gene Editing for Muscle Disorders Using Virus-Like Particles

AI simplified

CRISPR Gene Editing on OpenScience ↗PubMed ↗DOI ↗OA ↗

Abstract

Genetic problems in muscles can cause serious issues like difficulty moving and breathing. This research introduces a new method to deliver gene-editing tools directly to muscle cells using specially designed virus-like particles. These particles can carry different genetic materials and target muscle cells effectively. In tests on mice with Duchenne muscular dystrophy, the treatment corrected a specific genetic mutation and restored a critical protein, dystrophin, in various muscle types. As a result, the mice showed improved exercise abilities and endurance. This study paves the way for new gene editing techniques specifically for muscle diseases.

AI simplified

Muscle genetic defects can lead to impaired movement, respiratory failure, and other severe symptoms. The development of curative therapies is challenging due to the need for the delivery of gene-editing tools into skeletal muscle cells throughout the body. Here, we use muscular fusogens (Myomaker and Myomerger) to engineer muscle-specific virus-like particles (MuVLPs) for the systemic delivery of gene-editing tools. We demonstrate that MuVLPs can be loaded with diverse payloads, including EGFP, Cre and Cas9/sgRNA ribonucleoproteins (Cas9 RNPs), and can be delivered into skeletal muscle cells via targeted membrane fusion. Systemic administration of MuVLPs carrying Cas9 RNPs enables skeletal muscle-specific gene editing, which excised the exon containing a premature terminator codon mutation in a mouse model for Duchenne muscular dystrophy (DMD). This treatment restores dystrophin expression in various skeletal muscle tissues, including the diaphragm, quadriceps, tibialis anterior, gastrocnemius, and triceps. As a result, the treated mice exhibit a significantly increased capacity for exercise and endurance. This study established a platform for precise gene editing in skeletal muscle tissues.

Full Text

Full text is available at the source.

View full text (PDF) ↗View full text (HTML) ↗

Muscle-specific gene editing therapy via mammalian fusogen-directed virus-like particles

Abstract

Full Text

You found one interesting study. We’ll send the next 7.

what lands in your inbox each week:

Recent issues from the crispr gene editing brief