ArticleNature medicine2014
Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice.
Article in Nature medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT04240314 (Phase I/IIa Systemic Gene Delivery Clinical Trial of scAAV9.U7.ACCA for Exon 2 Duplication-Associated Duchenne Muscular Dystrophy), which is not on this map. Cited by 69 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.
Phase I/IIa Systemic Gene Delivery Clinical Trial of scAAV9.U7.ACCA for Exon 2 Duplication-Associated Duchenne Muscular Dystrophy
Who cites it
69 citing papers in PubMed, 118 citations in OpenAlex.
- Rare DMD Gene Duplication in a Lebanese Child With Duchene Muscular Dystrophy.Clinical case reports · 2026Article
- 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
- Exploring Therapies for Duchenne Muscular Dystrophy Using Transdifferentiated Patient Fibroblasts.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Genetic strategies for therapy of Duchenne muscular dystrophy.Molecular therapy. Nucleic acids · 2025Review
- AAV microdystrophin gene replacement therapy for Duchenne muscular dystrophy: progress and prospects.Gene therapy · 2025Review
- An engineered U7 small nuclear RNA scaffold greatly increases ADAR-mediated programmable RNA base editing.Nature communications · 2025Article
- Small but mighty: the rise of microprotein biology in neuroscience.Frontiers in molecular neuroscience · 2024Article
- Long-term dystrophin restoration supports development of splice correction therapy for DMD patients with exon 2 duplications.Molecular therapy. Methods & clinical development · 2023Article
- Persistence of exon 2 skipping and dystrophin expression at 18 months after U7snRNA-mediated therapy in the Dup2 mouse model.Molecular therapy. Methods & clinical development · 2023Article
- Therapeutic approaches for Duchenne muscular dystrophy.Nature reviews. Drug discovery · 2023Review
- RNA-Based Therapeutic Technology.International journal of molecular sciences · 2023Review
- Decoding the Gene Regulatory Network of Muscle Stem Cells in Mouse Duchenne Muscular Dystrophy: Revelations from Single-Nuclei RNA Sequencing Analysis.International journal of molecular sciences · 2023Article
- Recent Trends in Antisense Therapies for Duchenne Muscular Dystrophy.Pharmaceutics · 2023Review
- Review
- Current Strategies of Muscular Dystrophy Therapeutics: An Overview.Methods in molecular biology (Clifton, N.J.) · 2023Review
- Systematic analysis of copy number variants of uncertain significance partially overlapping with the haploinsufficient or triplosensitive genes in clinical testing.Annals of medicine · 2023Article
- Systemic PPMO-mediated dystrophin expression in the Dup2 mouse model of Duchenne muscular dystrophy.Molecular therapy. Nucleic acids · 2022Article
- Systemic delivery of an AAV9 exon-skipping vector significantly improves or prevents features of Duchenne muscular dystrophy in the Dup2 mouse.Molecular therapy. Methods & clinical development · 2022Article
- 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
- Intron mutations and early transcription termination in Duchenne and Becker muscular dystrophy.Human mutation · 2022Article
9 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
- Erratum issuedCorrigendum: Translation from a DMD exon 5 IRES results in a functional dystrophin isoform that attenuates dystrophinopathy in humans and mice.2015 · Brioschi, Simona [added]; Bovolenta, Matteo [added]; Neri, Marcella [added]
Authors and funding
25 authors at 10 institutions in 4 countries.
Funding
Abstract
Most mutations that truncate the reading frame of the DMD gene cause loss of dystrophin expression and lead to Duchenne muscular dystrophy. However, amelioration of disease severity has been shown to result from alternative translation initiation beginning in DMD exon 6 that leads to expression of a highly functional N-truncated dystrophin. Here we demonstrate that this isoform results from usage of an internal ribosome entry site (IRES) within exon 5 that is glucocorticoid inducible. We confirmed IRES activity by both peptide sequencing and ribosome profiling in muscle from individuals with minimal symptoms despite the presence of truncating mutations. We generated a truncated reading frame upstream of the IRES by exon skipping, which led to synthesis of a functional N-truncated isoform in both human subject-derived cell lines and in a new DMD mouse model, where expression of the truncated isoform protected muscle from contraction-induced injury and corrected muscle force to the same level as that observed in control mice. These results support a potential therapeutic approach for patients with mutations within the 5' exons of DMD.
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.