ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Terminal differentiation of cardiac and skeletal myocytes induces permissivity to AAV transduction by relieving inhibition imposed by DNA damage response proteins.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.
- Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays.International journal of molecular sciences · 2020Pooled it
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- Biomaterial-Based Nucleic Acid Delivery Systems for In Situ Tissue Engineering and Regenerative Medicine.International journal of molecular sciences · 2025Review
- A comprehensive analysis of scRNA-Seq and RNA-Seq unveils B cell immune suppression in the AAV-loaded brain.Immunologic research · 2025Article
- Precision genome editing using combinatorial viral vector delivery of CRISPR-Cas9 nucleases and donor DNA constructs.Nucleic acids research · 2025Article
- Cell Therapies and Gene Therapy for Diabetes: Current Progress.Current diabetes reviews · 2025Review
- Endothelial-to-mesenchymal transition enhances permissiveness to AAV vectors in cardiac endothelial cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- In vivo rescue of genetic dilated cardiomyopathy by systemic delivery of nexilin.Genome biology · 2024Article
- Casein kinase 2 activity is a host restriction factor for AAV transduction.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Identification of host essential factors for recombinant AAV transduction of the polarized human airway epithelium.Journal of virology · 2023Article
- Development of new adeno-associated virus capsid variants for targeted gene delivery to human cardiomyocytes.Molecular therapy. Methods & clinical development · 2023Article
- mNature aging · 2023Article
- Interactions between miRNAs and Double-Strand Breaks DNA Repair Genes, Pursuing a Fine-Tuning of Repair.International journal of molecular sciences · 2022Review
- Non-coding RNA therapeutics for cardiac regeneration.Cardiovascular research · 2021Review
- Insights into role of microRNAs in cardiac development, cardiac diseases, and developing novel therapies.Iranian journal of basic medical sciences · 2020Review
- AAV Vector Immunogenicity in Humans: A Long Journey to Successful Gene Transfer.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- Inducing Endogenous Cardiac Regeneration: Can Biomaterials Connect the Dots?Frontiers in bioengineering and biotechnology · 2020Review
- A GDF11/myostatin inhibitor, GDF11 propeptide-Fc, increases skeletal muscle mass and improves muscle strength in dystrophic mdx mice.Skeletal muscle · 2019Article
- Notch pathway activation enhances cardiosphere in vitro expansion.Journal of cellular and molecular medicine · 2018Article
- Depletion of the Insulator Protein CTCF Results in Herpes Simplex Virus 1 ReactivationJournal of virology · 2018Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Gene therapy vectors based on the adeno-associated virus (AAV) are extremely efficient for gene transfer into post-mitotic cells of heart, muscle, brain, and retina. The reason for their exquisite tropism for these cells has long remained elusive. Here, we show that upon terminal differentiation, cardiac and skeletal myocytes downregulate proteins of the DNA damage response (DDR) and that this markedly induces permissivity to AAV transduction. We observed that expression of members of the MRN complex (Mre11, Rad50, Nbs1), which bind the incoming AAV genomes, faded in cardiomyocytes at ~2 weeks after birth, as well as upon myoblast differentiation in vitro; in both cases, withdrawal of the cells from the cell cycle coincided with increased AAV permissivity. Treatment of proliferating cells with short-interfering RNAs (siRNAs) against the MRN proteins, or with microRNA-24, which is normally upregulated upon terminal differentiation and negatively controls the Nbs1 levels, significantly increased permissivity to AAV transduction. Consistently, delivery of these small RNAs to the juvenile liver concomitant with AAV markedly improved in vivo hepatocyte transduction. Collectively, these findings support the conclusion that cellular DDR proteins inhibit AAV transduction and that terminal cell differentiation relieves this restriction.
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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.