ArticleMolecular therapy : the journal of the American Society of Gene Therapy2021
DUX4 Transcript Knockdown with Antisense 2'-O-Methoxyethyl Gapmers for the Treatment of Facioscapulohumeral Muscular Dystrophy.
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 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Lipid nanoparticle delivery of antisense gapmers attenuates pathology in a mouse model of facioscapulohumeral muscular dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Article
- IncreasedInternational journal of molecular sciences · 2025Article
- Muscular Dystrophies.Advances in experimental medicine and biology · 2025Review
- Small nucleic acid drugs-the dawn of functional cure of chronic hepatitis B.Frontiers in pharmacology · 2025Review
- Molecular, Histological, and Functional Changes in Acta1-MCM;FLExDUX4/+ Mice.International journal of molecular sciences · 2024Article
- Oligonucleotide Therapies for Facioscapulohumeral Muscular Dystrophy: Current Preclinical Landscape.International journal of molecular sciences · 2024Review
- Systemic Pharmacotherapeutic Treatment of the ACTA1-MCM/FLExDUX4 Preclinical Mouse Model of FSHD.International journal of molecular sciences · 2024Article
- Flavones provide resistance to DUX4-induced toxicity via an mTor-independent mechanism.Cell death & disease · 2023Article
- A Systemically Administered Unconjugated Antisense Oligonucleotide Targeting DUX4 Improves Muscular Injury and Motor Function in FSHD Model Mice.Biomedicines · 2023Article
- Molecular and Phenotypic Changes in FLExDUX4 Mice.Journal of personalized medicine · 2023Article
- Long-Term Systemic Treatment of a Mouse Model Displaying Chronic FSHD-like Pathology with Antisense Therapeutics That InhibitBiomedicines · 2022Article
- FSHD Therapeutic Strategies: What Will It Take to Get to Clinic?Journal of personalized medicine · 2022Review
- Downstream events initiated by expression of FSHD-associated DUX4: Studies of nucleocytoplasmic transport, γH2AX accumulation, and Bax/Bak-dependence.Biology open · 2022Article
- RNA-based therapeutics for neurological diseases.RNA biology · 2022Review
- Systemic delivery of a DUX4-targeting antisense oligonucleotide to treat facioscapulohumeral muscular dystrophy.Molecular therapy. Nucleic acids · 2021Article
- Systemic antisense therapeutics inhibiting DUX4 expression ameliorates FSHD-like pathology in an FSHD mouse model.Human molecular genetics · 2021Article
- 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
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder characterized by a progressive, asymmetric weakening of muscles, starting with those in the upper body. It is caused by aberrant expression of the double homeobox protein 4 gene (DUX4) in skeletal muscle. FSHD is currently incurable. We propose to develop a therapy for FSHD using antisense 2'-O-methoxyethyl (2'-MOE) gapmers, to knock down DUX4 mRNA expression. Using immortalized patient-derived muscle cells and local intramuscular injections in the FLExDUX4 FSHD mouse model, we showed that our designed 2'-MOE gapmers significantly reduced DUX4 transcript levels in vitro and in vivo, respectively. Furthermore, in vitro, we observed significantly reduced expression of DUX4-activated downstream targets, restoration of FSHD signature genes by RNA sequencing, significant improvements in myotube morphology, and minimal off-target activity. This work facilitates the development of a promising candidate therapy for FSHD and lays down the foundation for in vivo systemic treatment studies.
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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.