Topoisomerase inhibition accelerates gene expression after adeno-associated virus-mediated gene transfer to the mammalian heart.

Topoisomerase inhibition accelerates gene expression after adeno-associated virus-mediated gene transfer to the mammalian heart. Research Abstract Details 

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Topoisomerase inhibition accelerates gene expression after adeno-associated virus-mediated gene transfer to the mammalian heart. Abstract Text:

Konkal-Matt R Prasad,Yaqin Xu,Zequan Yang,Marie-Claire Toufektsian,Stuart S Berr,Brent A French,

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<0.05). Southern blot analysis of AAV2 genomes in cardiac tissue showed rapid conversion of the AAV2 genome from its single-stranded to double-stranded form in CPT-treated mice. Non-invasive determinations of luciferase expression correlated well with in vitro luciferase assays. Direct injection of the AAV2 vector and long-term luciferase gene expression had no detectable effects on normal cardiac function as assessed by magnetic resonance imaging.

Topoisomerase inhibition accelerates gene expression after adeno-associated virus-mediated gene transfer to the mammalian heart. Publishing Authors By Initials

KM Prasad,Y Xu,Z Yang,MC Toufektsian,SS Berr,BA French,

For similar investigative techniques: genetic techniques: gene transfer techniques: transduction, genetic research abstracts see: investigative techniques: genetic techniques: gene transfer techniques: transduction, genetic research

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Topoisomerase inhibition accelerates gene expression after adeno-associated virus-mediated gene transfer to the mammalian heart. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Molecular therapy : the journal of the American So

VOLUME: 15

Page Numbers: 764-71

Journal Abbreviation: Mol. Ther.

ISSN: 1525-0016

DAY: 13

MONTH: 02

YEAR: 2007

Topoisomerase inhibition accelerates gene expression after adeno-associated virus-mediated gene transfer to the mammalian heart. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100890581

Topoisomerase inhibition accelerates gene expression after adeno-associated virus-mediated gene transfer to the mammalian heart. Keywords Mesh Terms:

KEYWORDS: Transduction, Genetic

MESH TERMS: genetics

Chemical & Substance for Abstract: Topoisomerase inhibition accelerates gene expression after adeno-associated virus-mediated gene transfer to the mammalian heart. Information

Substance Name: DNA Topoisomerases, Type I, Eukaryotic

Registry Number: EC 5.99.1.-

Grant and Affiliation Information for Topoisomerase inhibition accelerates gene expression after adeno-associated virus-mediated gene transfer to the mammalian heart.

AFFILIATION: Department of Biomedical Engineering, University of Virginia, Charlottesville, Virginia 22903, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: R01 HL58582

ACRONYM: HL

MEDLINETA: Mol Ther

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