Topoisomerase inhibition accelerates gene expression after adeno-associated virus-mediated gene transfer to the mammalian heart
| Autor: | Yaqin Xu, Zequan Yang, Konkal-Matt R Prasad, Brent A. French, Stuart S. Berr, Marie-Claire Toufektsian |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Male
viruses Genetic enhancement Genetic Vectors Gene Expression Coronary Disease Biology In Vitro Techniques medicine.disease_cause 03 medical and health sciences Transduction (genetics) Mice 0302 clinical medicine In vivo Luciferases Firefly Transduction Genetic Gene expression Drug Discovery medicine Genetics Bioluminescence imaging Animals Luciferase Enzyme Inhibitors Adeno-associated virus Molecular Biology 030304 developmental biology DNA Primers Pharmacology 0303 health sciences Base Sequence Topoisomerase Myocardium Genetic Therapy Dependovirus Molecular biology Recombinant Proteins 3. Good health Mice Inbred C57BL 030220 oncology & carcinogenesis Luminescent Measurements biology.protein Molecular Medicine Camptothecin Topoisomerase I Inhibitors |
| Zdroj: | Molecular therapy : the journal of the American Society of Gene Therapy. 15(4) |
| ISSN: | 1525-0016 |
| Popis: | Utility of adeno-associated virus 2 (AAV2) vectors for cardiac gene therapy is limited by the prolonged lag phase before maximal gene expression. Topoisomerase inhibition can induce AAV2-mediated gene expression in vivo, but with variable success in different tissues. In this study, we demonstrate that topoisomerase inhibition can accelerate AAV2-mediated gene expression in the mouse heart. We used an AAV2 vector expressing firefly luciferase and monitored expression kinetics using non-invasive bioluminescence imaging. In the group receiving vector alone, cardiac luciferase activity was evident from week 2 onward and increased progressively to reach a steady plateau by 9 weeks postinjection. In the group receiving vector and camptothecine (CPT), luciferase expression was evident from days 2 to 4 onward and increased rapidly to reach a steady plateau by 3-4 weeks postinjection, nearly three times faster than in the absence of CPT (P |
| Databáze: | OpenAIRE |
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