ArticleJCI insight2018
AAV CRISPR editing rescues cardiac and muscle function for 18 months in dystrophic mice.
Article in JCI insight, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 76 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
76 citing papers in PubMed, 1 synthesis or guideline pooled it, 97 citations in OpenAlex.
- Dilated cardiomyopathy as the initial presentation of Becker muscular dystrophy: a systematic review of published cases.Orphanet journal of rare diseases · 2022Pooled it
- Treatment with the Nox1/4 inhibitor Setanaxib ameliorates cardiac function in mouse models of Duchenne muscular dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Age-Dependent Effect of Myostatin Blockade in theMuscles (Basel, Switzerland) · 2026Article
- SORT LNPs encapsulating Cas9 mRNA achieve efficient editing in skeletal muscle in a dystrophic mouse model.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Myonuclear Domain-Associated and Central Nucleation-Dependent Spatial Restriction of Dystrophin Protein Expression.Journal of cachexia, sarcopenia and muscle · 2026Article
- Intravenous rAAV9 Produces Time-Resolved Parenchymal Labeling Downstream of the Vasculature in Adult Mice.Biology · 2026Article
- Genetic strategies for therapy of Duchenne muscular dystrophy.Molecular therapy. Nucleic acids · 2025Review
- Review
- Enhancing Specificity, Precision, Accessibility, Flexibility, and Safety to Overcome Traditional CRISPR/Cas Editing Challenges and Shape Future Innovations.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Treating neuromuscular diseases: unveiling gene therapy breakthroughs and pioneering future applications.Journal of biomedical science · 2025Review
- Gene Editing for Duchenne Muscular Dystrophy: From Experimental Models to Emerging Therapies.Degenerative neurological and neuromuscular disease · 2025Review
- From bench to bedside: cutting-edge applications of base editing and prime editing in precision medicine.Journal of translational medicine · 2024Review
- Comprehensive analysis of off-target and on-target effects resulting from liver-directed CRISPR-Cas9-mediated gene targeting with AAV vectors.Molecular therapy. Methods & clinical development · 2024Article
- Review
- Correction of human nonsense mutation via adenine base editing for Duchenne muscular dystrophy treatment in mouse.Molecular therapy. Nucleic acids · 2024Article
- Review
- Evolving Therapeutic Options for the Treatment of Duchenne Muscular Dystrophy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2023Review
- CRISPR-Editing Therapy for Duchenne Muscular Dystrophy.Human gene therapy · 2023Review
- Gene editing innovations and their applications in cardiomyopathy research.Disease models & mechanisms · 2023Review
- Hypoxia-induced tracheal elasticity in vector beetle facilitates the loading of pinewood nematode.eLife · 2023Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 2 countries.
Funding
Abstract
Adeno-associated virus-mediated (AAV-mediated) CRISPR editing is a revolutionary approach for treating inherited diseases. Sustained, often life-long mutation correction is required for treating these diseases. Unfortunately, this has never been demonstrated with AAV CRISPR therapy. We addressed this question in the mdx model of Duchenne muscular dystrophy (DMD). DMD is caused by dystrophin gene mutation. Dystrophin deficiency leads to ambulation loss and cardiomyopathy. We treated 6-week-old mice intravenously and evaluated disease rescue at 18 months. Surprisingly, nominal dystrophin was restored in skeletal muscle. Cardiac dystrophin was restored, but histology and hemodynamics were not improved. To determine the underlying mechanism, we evaluated components of the CRISPR-editing machinery. Intriguingly, we found disproportional guide RNA (gRNA) vector depletion. To test whether this is responsible for the poor outcome, we increased the gRNA vector dose and repeated the study. This strategy significantly increased dystrophin restoration and reduced fibrosis in all striated muscles at 18 months. Importantly, skeletal muscle function and cardiac hemodynamics were significantly enhanced. Interestingly, we did not see selective depletion of the gRNA vector after intramuscular injection. Our results suggest that gRNA vector loss is a unique barrier for systemic AAV CRISPR therapy. This can be circumvented by vector dose optimization.
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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.