ArticleNature communications2024
AAV delivery strategy with mechanical support for safe and efficacious cardiac gene transfer in swine.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Signaling pathways regulating cardiac regeneration.Cell regeneration (London, England) · 2026Review
- Gene Therapy for Cardiovascular and Cerebrovascular Disease: Mechanisms, Translational Barriers, and the Road Ahead.Biomedicines · 2026Review
- Cardiac epigenome in heart development and disease.Nature reviews. Cardiology · 2026Review
- Gene Therapies in Atrial Fibrillation.Journal of cardiovascular translational research · 2025Review
- Cardiac gene therapy makes a comeback.Nature medicine · 2025Article
- Myocardial infarction creates a critical time window for AAV-based cardiac gene transfer.Fundamental research · 2025Article
- LMNA-related cardiomyopathy: From molecular pathology to cardiac gene therapy.Journal of advanced research · 2025Review
- Gene therapy in cardiac and vascular diseases: a review of approaches to treat genetic and common cardiovascular diseases with novel gene-based therapeutics.Cardiovascular research · 2025Review
- PERM1 Gene Delivery via AAV Prevents Heart Failure in a Mouse Model of Pressure Overload.bioRxiv : the preprint server for biology · 2025Article
- AAV6 vectors provide superior gene transfer compared to AAV9 vectors following intramyocardial administration.Molecular therapy. Methods & clinical development · 2025Article
- Gene Therapy for Cardiac Arrhythmias: Mechanisms, Modalities and Therapeutic Applications.Medical sciences (Basel, Switzerland) · 2025Review
- Linking oxidative stress biomarkers to disease progression and antioxidant therapy in hypertension and diabetes mellitus.Frontiers in molecular biosciences · 2025Review
- AAV viral vectors as therapeutic interventions for inherited or non-inherited cardiac disorders: current aspects and future prospects.Frontiers in medicine · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
Adeno-associated virus-based gene therapy is a promising avenue in heart failure treatment, but has shown limited cardiac virus uptake in humans, requiring new approaches for clinical translation. Using a Yorkshire swine ischemic heart failure model, we demonstrate significant improvement in gene uptake with temporary coronary occlusions assisted by mechanical circulatory support. We first show that mechanical support during coronary artery occlusions prevents hemodynamic deterioration (n = 5 female). Subsequent experiments show that coronary artery occlusions during gene delivery improve gene transduction, while adding coronary sinus occlusion (Stop-flow) further improves gene expression up to >1 million-fold relative to conventional intracoronary infusion. Complete survival during and after delivery (n = 10 female, n = 10 male) further indicates safety of the approach. Improved cardiac gene expression correlates with virus uptake without an increase in extra-cardiac expression. Stop-flow delivery of virus-sized gold nanoparticles exhibits enhanced endothelial adherence and uptake, suggesting a mechanism independent of virus biology. Together, utilizing mechanical support for cardiac gene delivery offers a clinically-applicable strategy for heart failure-targeted therapies.
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