ArticleMolecular therapy. Nucleic acids2013
Repair of Mybpc3 mRNA by 5'-trans-splicing in a Mouse Model of Hypertrophic Cardiomyopathy.
Article in Molecular therapy. Nucleic acids, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Cardiomyopathy phenotypes in human-induced pluripotent stem cell-derived cardiomyocytes-a systematic review.Pflugers Archiv : European journal of physiology · 2019Pooled it
- Therapeutic upregulation of gene expression in inherited cardiomyopathies from current approaches to future directions.Nature cardiovascular research · 2026Review
- Transcriptome Reprogramming in Heart Failure: The Hidden Splicing Code.Current cardiology reports · 2026Review
- RNA-Based Therapies for Treating Monogenic Cardiomyopathies.The Canadian journal of cardiology · 2026Review
- Perinatal death in pig models of hypertrophic cardiomyopathy carrying sarcomere pathogenic variants.Journal of molecular and cellular cardiology plus · 2025Article
- Cardiac Phase-Resolved TBiomedicines · 2025Article
- Experimental Models of Hypertrophic Cardiomyopathy: A Systematic Review.JACC. Basic to translational science · 2025Review
- Review
- Chronic Activation of Tubulin Tyrosination Improves Heart Function.Circulation research · 2024Article
- RNA exon editing: Splicing the way to treat human diseases.Molecular therapy. Nucleic acids · 2024Review
- Modeling hypertrophic cardiomyopathy with human cardiomyocytes derived from induced pluripotent stem cells.Stem cell research & therapy · 2022Review
- Targeted therapies in genetic dilated and hypertrophic cardiomyopathies: from molecular mechanisms to therapeutic targets. A position paper from the Heart Failure Association (HFA) and the Working Group on Myocardial Function of the European Society of Cardiology (ESC).European journal of heart failure · 2022Article
- Thin filament cardiomyopathies: A review of genetics, disease mechanisms, and emerging therapeutics.Frontiers in cardiovascular medicine · 2022Review
- Cardiac sarcomere mechanics in health and disease.Biophysical reviews · 2021Review
- Translational investigation of electrophysiology in hypertrophic cardiomyopathy.Journal of molecular and cellular cardiology · 2021Article
- Hypertrophic Cardiomyopathy: From Phenotype and Pathogenesis to Treatment.Frontiers in cardiovascular medicine · 2021Review
- Gene therapy for inherited arrhythmias.Cardiovascular research · 2020Review
- Alternative Management Options for Hypertrophic Cardiomyopathy: Feasible?JACC. Case reports · 2020Article
- RNA Splicing Defects in Hypertrophic Cardiomyopathy: Implications for Diagnosis and Therapy.International journal of molecular sciences · 2020Review
- Hypertrophic Cardiomyopathy: A Vicious Cycle Triggered by Sarcomere Mutations and Secondary Disease Hits.Antioxidants & redox signaling · 2019Review
Corrections and comments
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Authors and funding
14 authors at 7 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
RNA trans-splicing has been explored as a therapeutic option for a variety of genetic diseases, but not for cardiac genetic disease. Hypertrophic cardiomyopathy (HCM) is an autosomal-dominant disease, characterized by left ventricular hypertrophy (LVH) and diastolic dysfunction. MYBPC3, encoding cardiac myosin-binding protein C (cMyBP-C) is frequently mutated. We evaluated the 5'-trans-splicing strategy in a mouse model of HCM carrying a Mybpc3 mutation. 5'-trans-splicing was induced between two independently transcribed molecules, the mutant endogenous Mypbc3 pre-mRNA and an engineered pre-trans-splicing molecule (PTM) carrying a FLAG-tagged wild-type (WT) Mybpc3 cDNA sequence. PTMs were packaged into adeno-associated virus (AAV) for transduction of cultured cardiac myocytes and the heart in vivo. Full-length repaired Mybpc3 mRNA represented up to 66% of total Mybpc3 transcripts in cardiac myocytes and 0.14% in the heart. Repaired cMyBP-C protein was detected by immunoprecipitation in cells and in vivo and exhibited correct incorporation into the sarcomere in cardiac myocytes. This study provides (i) the first evidence of successful 5'-trans-splicing in vivo and (ii) proof-of-concept of mRNA repair in the most prevalent cardiac genetic disease. Since current therapeutic options for HCM only alleviate symptoms, these findings open new horizons for causal therapy of the severe forms of the disease.Molecular Therapy-Nucleic Acids (2013) 2, e102; doi:10.1038/mtna.2013.31; published online 2 July 2013.
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Registered trials
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