ArticleJournal of translational medicine2020
Comparative analysis of adeno-associated virus serotypes for gene transfer in organotypic heart slices.
Article in Journal of translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Patient-derived tissue cultures complement neurospheres for preclinical evaluation of AAV-mediated gene delivery in glioblastoma.Journal of neuro-oncology · 2026Article
- Advances in Living Myocardial Slice Technology for Heart Failure Research.Current heart failure reports · 2026Review
- AAV6 vectors provide superior gene transfer compared to AAV9 vectors following intramyocardial administration.Molecular therapy. Methods & clinical development · 2025Article
- Living myocardial slices as a model for testing cardiac pro-reparative gene therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Therapeutic Application and Structural Features of Adeno-Associated Virus Vector.Current issues in molecular biology · 2024Review
- Contractility measurements for cardiotoxicity screening with ventricular myocardial slices of pigs.Cardiovascular research · 2023Article
- Development of new adeno-associated virus capsid variants for targeted gene delivery to human cardiomyocytes.Molecular therapy. Methods & clinical development · 2023Article
- Cellular reprogramming of fibroblasts in heart regeneration.Journal of molecular and cellular cardiology · 2023Review
- Culture of vibrating microtome tissue slices as a 3D model in biomedical research.Journal of biological engineering · 2023Review
- Living myocardial slices for the study of nucleic acid-based therapies.Frontiers in bioengineering and biotechnology · 2023Article
- Living myocardial slices: Advancing arrhythmia research.Frontiers in physiology · 2023Review
- AAV vectors: The Rubik's cube of human gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- AAV2-VEGF-B gene therapy failed to induce angiogenesis in ischemic porcine myocardium due to inflammatory responses.Gene therapy · 2022Article
- Skeletal muscle derived Musclin protects the heart during pathological overload.Nature communications · 2022Article
- Potential Applications for Targeted Gene Therapy to Protect Against Anthracycline Cardiotoxicity:JACC. CardioOncology · 2021Review
- Cardiomyocytes Cellular Phenotypes After Myocardial Infarction.Frontiers in cardiovascular medicine · 2021Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundVectors derived from adeno-associated viruses (AAVs) are widely used for gene transfer both in vitro and in vivo and have gained increasing interest as shuttle systems to deliver therapeutic genes to the heart. However, there is little information on their tissue penetration and cytotoxicity, as well as the optimal AAV serotype for transferring genes to diseased hearts. Therefore, we aimed to establish an organotypic heart slice culture system for mouse left ventricular (LV) myocardium and use this platform to analyze gene transfer efficiency, cell tropism, and toxicity of different AAV serotypes.
methodsLV tissue slices, 300 µm thick, were prepared from 15- to 17-day-old transgenic alpha-myosin heavy-chain-mCherry mice using a vibrating microtome. Tissue slice viability in air-liquid culture was evaluated by calcein-acetoxymethyl ester staining, mCherry fluorescence intensity, and the tetrazolium assay. Four recombinant AAV serotypes (1, 2, 6, 8) expressing green fluorescent protein (GFP) under the CAG promoter were added to the slice surface. Gene transfer efficiency was quantified as the number of GFP-positive cells per slice. AAV cell tropism was examined by comparing the number of GFP-positive cardiomyocytes (CMs) and fibroblasts within heart slices.
resultsSlices retained viability in in vitro culture for at least 5 days. After adding AAV particles, AAV6-infected slices showed the highest number of GFP-expressing cells, almost exclusively CMs. Slice incubation with AAV1, 2, and 8 resulted in fewer GFP-positive cells, with AAV2 having the lowest gene transfer efficiency. None of the AAV serotypes tested caused significant cytotoxicity when compared to non-infected control slices.
conclusionsWe have established a readily available mouse organotypic heart slice culture model and provided evidence that AAV6 may be a promising gene therapy vector for heart failure and other cardiac diseases.
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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 Socratic graph.