| A Single Direct Injection into the Left Ventricular Wall of an AAV9 Vector Expressing EcSOD from the Cardiac Troponin-T Promoter Protects Mice Against Myocardial Infarction. | |
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MedLine Citation:
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PMID: 21674736 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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BACKGROUND: Localized administration of a highly efficient gene delivery system in combination with a cardiac-selective promoter may provide a favorable biosafety profile in clinical applications such as coronary artery bypass graft surgery (CABG), where regions of myocardium can be readily injected to protect them against the potential threat of future ischemic events. METHODS: AAV vectors expressing luciferase or eGFP packaged into AAV serotypes 1, 2, 6, 8 and 9 were injected into the left ventricular (LV) wall of adult mice to determine the time course, magnitude and distribution of gene expression. An AAV9 vector expressing extracellular superoxide dismutase (EcSOD) from the cTnT promoter was then directly injected into the LV wall of adult mice. Myocardial infarction (MI) was induced 4 weeks after injection and infarct size was determined by TTC and Phthalo blue staining. RESULTS: Serotypes AAV 9, 8, 1 and 6 provided early onset of gene expression in the heart with minimal extra-cardiac gene expression. AAV9 provided the highest magnitude of gene expression. Immunostaining for eGFP showed expression spanning the anterior to posterior walls from the mid ventricle to the apex. A single direct injection of the AAV9 vector bearing EcSOD (n = 5) decreased the mean infarct size by 50% as compared to the eGFP control group (n = 8) (44 ± 7% vs 22 ± 5%, p = 0.04). CONCLUSIONS: AAV serotype 9 is highly efficient for cardiac gene delivery, as evidenced by early onset and high-level gene expression. AAV9 mediated, cardiac selective overexpression of EcSOD from the cTnT promoter significantly reduced infarct size in mice. AAV, gene therapy, cardiac-selective promoter, myocardial infarction, cardioprotection, EcSOD Copyright © 2011 John Wiley & Sons, Ltd. |
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Authors:
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Konkal-Matt R Prasad; Robert S Smith; Yaqin Xu; Brent A French |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-6-14 |
Journal Detail:
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Title: The journal of gene medicine Volume: - ISSN: 1521-2254 ISO Abbreviation: - Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-6-15 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9815764 Medline TA: J Gene Med Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 John Wiley & Sons, Ltd. |
Affiliation:
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Department of Biomedical Engineering, University of Virginia, Charlottesville, VA, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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