ArticleThe journal of gene medicine
Adeno-associated virus serotype 9 administered systemically after reperfusion preferentially targets cardiomyocytes in the infarct border zone with pharmacodynamics suitable for the attenuation of left ventricular remodeling.
Article in The journal of gene medicine. 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, 25 citations in OpenAlex.
- Unifying and unique roles of non-coding RNA biomarkers in liver and heart fibrosis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Review
- CPT1a Expression Is a Critical Cardioprotective Response to Pathological Stress That Enables Rescue by Gene Transfer.Circulation research · 2026Article
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- CITED4 gene therapy protects against maladaptive cardiac remodeling after ischemia/reperfusion injury in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Targeting mAKAPβ expression as a therapeutic approach for ischemic cardiomyopathy.Gene therapy · 2023Article
- Distribution of cardiomyocyte-selective adeno-associated virus serotype 9 vectors in swine following intracoronary and intravenous infusion.Physiological genomics · 2022Article
- Non-viral vector based gene transfection with human induced pluripotent stem cells derived cardiomyocytes.Scientific reports · 2019Article
- Therapeutic potential of AAV9-S15D-RLC gene delivery in humanized MYL2 mouse model of HCM.Journal of molecular medicine (Berlin, Germany) · 2019Article
- Systemic injection of AAV9 carrying a periostin promoter targets gene expression to a myofibroblast-like lineage in mouse hearts after reperfused myocardial infarction.Gene therapy · 2016Article
- A novel cardiac muscle-derived biomaterial reduces dyskinesia and postinfarct left ventricular remodeling in a mouse model of myocardial infarction.Physiological reports · 2015Article
- Enhanced skeletal muscle expression of extracellular superoxide dismutase mitigates streptozotocin-induced diabetic cardiomyopathy by reducing oxidative stress and aberrant cell signaling.Circulation. Heart failure · 2015Article
- Systemic delivery of shRNA by AAV9 provides highly efficient knockdown of ubiquitously expressed GFP in mouse heart, but not liver.PloS one · 2013Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundAdeno-associated virus serotype 9 (AAV9) vectors provide efficient and uniform gene expression to normal myocardium following systemic administration, with kinetics that approach steady-state within 2-3 weeks. However, as a result of the delayed onset of gene expression, AAV vectors have not previously been administered intravenously after reperfusion for post-infarct gene therapy applications. The present study evaluated the therapeutic potential of post-myocardial infarction gene delivery using intravenous AAV9.
methodsAAV9 vectors expressing firefly luciferase, enhanced green fluorescent protein (eGFP) or extracellular superoxide dismutase genes from the cardiac troponin-T (cTnT) promoter (AcTnTLuc, AcTnTeGFP, AcTnTEcSOD) were employed. AcTnTLuc was administered intravenously at 10 min and at 1, 2 and 3 days post-ischemia/reperfusion (IR), and the kinetics of luciferase expression were assessed with bioluminescence imaging. AcTnTeGFP was used to evaluate the distribution of eGFP expression. High-resolution echocardiography was used to evaluate the effects of AcTnTEcSOD on left ventricular (LV) remodeling when injected 10 min post-IR.
resultsCompared to sham animals, luciferase expression at 2 days after vector administration was elevated by four-, 24-, 210- and 213-fold in groups injected at 10 min, 1 day, 2 days and 3 days post-IR, respectively. The expression of cTnT-driven eGFP was strongest in cardiomyocytes bordering the infarct zone. In the efficacy study of EcSOD, post-infarct LV end-systolic and end-diastolic volumes at days 14 and 28 were significantly smaller in the EcSOD group compared to the control.
conclusionsSystemic administration of AAV9 vectors after IR both elevates and accelerates gene expression that preferentially targets cardiomyocytes in the border zone with pharmacodynamics suitable for the attenuation of LV remodeling.
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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 OpenQuestion graph.