ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
AAV6-mediated systemic shRNA delivery reverses disease in a mouse model of facioscapulohumeral muscular dystrophy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 48 citations in OpenAlex.
- Delivery of genetic medicines for muscular dystrophies.Cell reports. Medicine · 2025Review
- Genetic Approaches for the Treatment of Facioscapulohumeral Muscular Dystrophy.Frontiers in pharmacology · 2021Review
- Current Genetic Survey and Potential Gene-Targeting Therapeutics for Neuromuscular Diseases.International journal of molecular sciences · 2020Review
- In vivo engineering of lymphocytes after systemic exosome-associated AAV delivery.Scientific reports · 2020Article
- Endogenous MicroRNA Competition as a Mechanism of shRNA-Induced Cardiotoxicity.Molecular therapy. Nucleic acids · 2020Article
- HyPer2 imaging reveals temporal and heterogeneous hydrogen peroxide changes in denervated and aged skeletal muscle fibers in vivo.Scientific reports · 2019Article
- Facioscapulohumeral dystrophy: activating an early embryonic transcriptional program in human skeletal muscle.Human molecular genetics · 2018Review
- A Pediatric Review of Facioscapulohumeral Muscular Dystrophy.Journal of pediatric neurology : JPN · 2018Article
- Pre-clinical Safety and Off-Target Studies to Support Translation of AAV-Mediated RNAi Therapy for FSHD.Molecular therapy. Methods & clinical development · 2018Article
- Genome engineering: a new approach to gene therapy for neuromuscular disorders.Nature reviews. Neurology · 2017Review
- Future of rAAV Gene Therapy: Platform for RNAi, Gene Editing, and Beyond.Human gene therapy · 2017Article
- Systemic delivery of adeno-associated viral vectors.Current opinion in virology · 2016Review
- Targeting mRNA for the treatment of facioscapulohumeral muscular dystrophy.Intractable & rare diseases research · 2016Review
- Therapeutic impact of systemic AAV-mediated RNA interference in a mouse model of myotonic dystrophy.Human molecular genetics · 2015Article
- Differential myofiber-type transduction preference of adeno-associated virus serotypes 6 and 9.Skeletal muscle · 2015Article
- The potential of adeno-associated viral vectors for gene delivery to muscle tissue.Expert opinion on drug delivery · 2014Review
- Morpholino treatment improves muscle function and pathology of Pitx1 transgenic mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Influence of immune responses in gene/stem cell therapies for muscular dystrophies.BioMed research international · 2014Review
- Facioscapulohumeral dystrophy: the path to consensus on pathophysiology.Skeletal muscle · 2014Review
- Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
Abstract
Treatment of dominantly inherited muscle disorders remains a difficult task considering the need to eliminate the pathogenic gene product in a body-wide fashion. We show here that it is possible to reverse dominant muscle disease in a mouse model of facioscapulohumeral muscular dystrophy (FSHD). FSHD is a common form of muscular dystrophy associated with a complex cascade of epigenetic events following reduction in copy number of D4Z4 macrosatellite repeats located on chromosome 4q35. Several 4q35 genes have been examined for their role in disease, including FRG1. Overexpression of FRG1 causes features related to FSHD in transgenic mice and the FRG1 mouse is currently the only available mouse model of FSHD. Here we show that systemic delivery of RNA interference expression cassettes in the FRG1 mouse, after the onset of disease, led to a dose-dependent long-term FRG1 knockdown without signs of toxicity. Histological features including centrally nucleated fibers, fiber size reduction, fibrosis, adipocyte accumulation, and inflammation were all significantly improved. FRG1 mRNA knockdown resulted in a dramatic restoration of muscle function. Through RNA interference (RNAi) expression cassette redesign, our method is amenable to targeting any pathogenic gene offering a viable option for long-term, body-wide treatment of dominant muscle disease in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.