ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
Dystrophin Gene-Editing Stability Is Dependent on Dystrophin Levels in Skeletal but Not Cardiac Muscles.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 24 citations in OpenAlex.
- Functional editing of the OTC locus by targeted integration with phenotype correction and restoration of endogenous expression patterns.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Duchenne muscular dystrophy: from gene to gene-ius therapies.Skeletal muscle · 2026Review
- Article
- From molecular correction to functional rescue: delivery, tissue state, and immunobiology as the principal constraints on dystrophin-restoring therapy in Duchenne muscular dystrophy.Frontiers in pharmacology · 2026Review
- Genetic strategies for therapy of Duchenne muscular dystrophy.Molecular therapy. Nucleic acids · 2025Review
- The road toward AAV-mediated gene therapy of Duchenne muscular dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Advances in Duchenne Muscular Dystrophy: Diagnostic Techniques and Dystrophin Domain Insights.International journal of molecular sciences · 2025Review
- Gene Editing for Duchenne Muscular Dystrophy: From Experimental Models to Emerging Therapies.Degenerative neurological and neuromuscular disease · 2025Review
- Upregulation of utrophin improves the phenotype of Duchenne muscular dystrophy hiPSC-derived CMs.Molecular therapy. Nucleic acids · 2024Article
- Have a Little Heart (or Not): Highly Minimized Skeletal Muscle Regulatory Cassettes with Low or No Activity in the Heart.Human gene therapy · 2024Article
- Article
- Correction of human nonsense mutation via adenine base editing for Duchenne muscular dystrophy treatment in mouse.Molecular therapy. Nucleic acids · 2024Article
- Review
- Dystrophin- and Utrophin-Based Therapeutic Approaches for Treatment of Duchenne Muscular Dystrophy: A Comparative Review.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- CRISPR-Cas9 homology-independent targeted integration of exons 1-19 restores full-length dystrophin in mice.Molecular therapy. Methods & clinical development · 2023Article
- The Role of Mitochondria in Mediation of Skeletal Muscle Repair.Muscles (Basel, Switzerland) · 2023Review
- Review
- Comparison of dystrophin expression following gene editing and gene replacement in an aged preclinical DMD animal model.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- The gRNA Vector Level Determines the Outcome of Systemic AAV CRISPR Therapy for Duchenne Muscular Dystrophy.Human gene therapy · 2022Article
- CRISPR Therapeutics for Duchenne Muscular Dystrophy.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Gene editing is often touted as a permanent method for correcting mutations, but its long-term benefits in Duchenne muscular dystrophy (DMD) may depend on sufficiently high editing efficiencies to halt muscle degeneration. Here, we explored the persistence of dystrophin expression following recombinant adeno-associated virus serotype 6 (rAAV6):CRISPR-Cas9-mediated multi-exon deletion/reframing in systemically injected 2- and 11-week-old dystrophic mice and show that induction of low dystrophin levels persists for several months in cardiomyocytes but not in skeletal muscles, where myofibers remain susceptible to necrosis and regeneration. Whereas gene-correction efficiency in both muscle types was enhanced with increased ratios of guide RNA (gRNA)-to-nuclease vectors, obtaining high dystrophin levels in skeletal muscles via multi-exon deletion remained challenging. In contrast, when AAV-microdystrophin was codelivered with editing components, long-term gene-edited dystrophins persisted in both muscle types. These results suggest that the high rate of necrosis and regeneration in skeletal muscles, compared with the relative stability of dystrophic cardiomyocytes, caused the rapid loss of edited genomes. Consequently, stable dystrophin expression in DMD skeletal muscles will require either highly efficient gene editing or the use of cotreatments that decrease skeletal muscle degeneration.
Indexed as
Identifiers
What OpenQuestion holds
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.