ArticleMolecular therapy. Nucleic acids2017
Antisense Oligonucleotides Promote Exon Inclusion and Correct the Common c.-32-13T>G GAA Splicing Variant in Pompe Disease.
Article in Molecular therapy. Nucleic acids, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Are Anti-rhGAA Antibodies a Determinant of Treatment Outcome in Adults with Late-Onset Pompe Disease? A Systematic Review.Biomolecules · 2023Pooled it
- The ACE I/D polymorphism does not explain heterogeneity of natural course and response to enzyme replacement therapy in Pompe disease.PloS one · 2018Trial
- A Comprehensive Update on Pompe Disease: From Existing Therapies to Emerging Curative Strategies.International journal of molecular sciences · 2026Review
- Pompe Disease: Pathogenesis, Molecular Mechanisms, Neurological Aspects, Diagnostics and Modern Therapeutic Approaches.International journal of molecular sciences · 2026Review
- Splicing correction by peptide-conjugated morpholinos as a novel treatment for late-onset Pompe disease.Molecular therapy. Nucleic acids · 2025Article
- Skeletal muscle effects of antisense oligonucleotides targeting glycogen synthase 1 in a mouse model of Pompe disease.Clinical and translational medicine · 2025Article
- Expansion of Splice-Switching Therapy with Antisense Oligonucleotides.International journal of molecular sciences · 2025Review
- Management of Pompe disease alongside and beyond ERT: a narrative review.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2025Review
- Rescue of common and rare exon 2 skipping variants of the GAA gene using modified U1 snRNA.Molecular medicine (Cambridge, Mass.) · 2025Article
- Exploring precision treatments in immune-mediated inflammatory diseases: Harnessing the infinite potential of nucleic acid delivery.Exploration (Beijing, China) · 2025Review
- Highlights of Precision Medicine, Genetics, Epigenetics and Artificial Intelligence in Pompe Disease.International journal of molecular sciences · 2025Review
- Case Report: Incidental late-onset Pompe disease diagnosis in a man with no clinical and instrumental evidence of neuromuscular dysfunction.Frontiers in genetics · 2025Article
- Noncoding variants are a rare cause of recessive developmental disorders in trans with coding variants.Genetics in medicine : official journal of the American College of Medical Genetics · 2024Article
- Advances in Pompe Disease Treatment: From Enzyme Replacement to Gene Therapy.Molecular diagnosis & therapy · 2024Review
- Potential of Cell-Penetrating Peptide-Conjugated Antisense Oligonucleotides for the Treatment of SMA.Molecules (Basel, Switzerland) · 2024Review
- Splice-Modulating Antisense Oligonucleotides as Therapeutics for Inherited Metabolic Diseases.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- QR-1011 restores defective ABCA4 splicing caused by multiple severe ABCA4 variants underlying Stargardt disease.Scientific reports · 2024Article
- Practical Recommendations for the Selection of Patients for Individualized Splice-Switching ASO-Based Treatments.Human mutation · 2024Review
- RNA-Based Therapeutic Technology.International journal of molecular sciences · 2023Review
- Home-Based Infusion of Alglucosidase Alfa Can Safely be Implemented in Adults with Late-Onset Pompe Disease: Lessons Learned from 18,380 Infusions.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The most common variant causing Pompe disease is c.-32-13T>G (IVS1) in the acid α-glucosidase (GAA) gene, which weakens the splice acceptor of GAA exon 2 and induces partial and complete exon 2 skipping. It also allows a low level of leaky wild-type splicing, leading to a childhood/adult phenotype. We hypothesized that cis-acting splicing motifs may exist that could be blocked using antisense oligonucleotides (AONs) to promote exon inclusion. To test this, a screen was performed in patient-derived primary fibroblasts using a tiling array of U7 small nuclear RNA (snRNA)-based AONs. This resulted in the identification of a splicing regulatory element in GAA intron 1. We designed phosphorodiamidate morpholino oligomer-based AONs to this element, and these promoted exon 2 inclusion and enhanced GAA enzyme activity to levels above the disease threshold. These results indicate that the common IVS1 GAA splicing variant in Pompe disease is subject to negative regulation, and inhibition of a splicing regulatory element using AONs is able to restore canonical GAA splicing and endogenous GAA enzyme activity.
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