ArticleMolecular therapy. Nucleic acids2017
Evaluation of MYBPC3 trans-Splicing and Gene Replacement as Therapeutic Options in Human iPSC-Derived Cardiomyocytes.
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 67 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 104 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
- Variable cMyBP-C expression from cell to cell in a MYBPC3Stem cell research & therapy · 2026Article
- RNA-Based Therapies for Treating Monogenic Cardiomyopathies.The Canadian journal of cardiology · 2026Review
- CRISPR-based Transcriptional Regulation: Technologies, Applications, and Future Directions.DNA · 2025Article
- Current and emerging medical and surgical therapy in hypertrophic cardiomyopathy.Journal of cardiovascular imaging · 2025Review
- Dissecting cardiovascular disease-associated noncoding genetic variants using human iPSC models.Stem cell reports · 2025Review
- AAV9-mediated MYBPC3 gene therapy with optimized expression cassette enhances cardiac function and survival in MYBPC3 cardiomyopathy models.Nature communications · 2025Article
- State of the art and perspectives of gene therapy in heart failure. A scientific statement of the Heart Failure Association of the ESC, the ESC Council on Cardiovascular Genomics and the ESC Working Group on Myocardial & Pericardial Diseases.European journal of heart failure · 2025Review
- Unveiling the Future of Cardiac Care: A Review of Gene Therapy in Cardiomyopathies.International journal of molecular sciences · 2024Review
- 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
- Efficient and reproducible generation of human iPSC-derived cardiomyocytes and cardiac organoids in stirred suspension systems.Nature communications · 2024Article
- Article
- Genetic Mutations and Mitochondrial Redox Signaling as Modulating Factors in Hypertrophic Cardiomyopathy: A Scoping Review.International journal of molecular sciences · 2024Article
- Efficient and reproducible generation of human iPSC-derived cardiomyocytes using a stirred bioreactor.bioRxiv : the preprint server for biology · 2024Article
- An overview of the treatments for hypertrophic cardiomyopathy.Frontiers in cardiovascular medicine · 2024Review
- Article
- Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene therapy is a promising option for severe forms of genetic diseases. We previously provided evidence for the feasibility of trans-splicing, exon skipping, and gene replacement in a mouse model of hypertrophic cardiomyopathy (HCM) carrying a mutation in MYBPC3, encoding cardiac myosin-binding protein C (cMyBP-C). Here we used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from an HCM patient carrying a heterozygous c.1358-1359insC MYBPC3 mutation and from a healthy donor. HCM hiPSC-CMs exhibited ∼50% lower MYBPC3 mRNA and cMyBP-C protein levels than control, no truncated cMyBP-C, larger cell size, and altered gene expression, thus reproducing human HCM features. We evaluated RNA trans-splicing and gene replacement after transducing hiPSC-CMs with adeno-associated virus. trans-splicing with 5' or 3' pre-trans-splicing molecules represented ∼1% of total MYBPC3 transcripts in healthy hiPSC-CMs. In contrast, gene replacement with the full-length MYBPC3 cDNA resulted in ∼2.5-fold higher MYBPC3 mRNA levels in HCM and control hiPSC-CMs. This restored the cMyBP-C level to 81% of the control level, suppressed hypertrophy, and partially restored gene expression to control level in HCM cells. This study provides evidence for (1) the feasibility of trans-splicing, although with low efficiency, and (2) efficient gene replacement in hiPSC-CMs with a MYBPC3 mutation.
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