Efficient and Durable Gene Transfer to Transplanted Heart Using Adeno-associated Virus 9 Vector

Naoto Miyagi, Vinay P. Rao, Davide Ricci, Zeji Du, Guerard W. Byrne, Kent R Bailey, Hiroyuki Nakai, Stephen J Russell, Christopher G A McGregor

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: In this investigation we studied the efficacy and durability of recombinant adeno-associated virus serotype 9 (rAAV9) vector-mediated gene transfer to the transplanted rat heart. Methods: A rAAV9-CMV-lacZ vector diluted in cold (4°C) University of Wisconsin solution was used to perfuse the rat coronary vasculature for 20 minutes prior to syngeneic heterotopic transplantation. Perfusion experiments (six groups, n = 3/group) were performed without rAAV9 and at four separate doses ranging from 2 × 109 to 2 × 1012 viral genomes/ml. The transplanted heart was recovered 10 days or 3 months after transplantation and expression of lacZ assessed by histology, enzyme-linked immunoassay and real-time reverse transcript-polymerase chain reaction (RT-PCR). In a final group (n = 3), rAAV9 was administered systemically to compare the cardiac transduction efficiency and viral distribution to other organs. Results: Transduction efficiency of perfused virus correlated with vector dose (p < 0.0001), with myocardial transduction ranging up to 71.74% at the highest dose. Cardiac expression of lacZ was equivalent at 10 days and 3 months. There was no evidence of viral gene transfer to other organs after heart transplantation. Conclusions: Our findings demonstrate efficient and durable rAAV9-mediated gene transfer to the transplanted heart after ex vivo perfusion and suggest that AAV9 is a promising vector for cardiac gene therapy.

Original languageEnglish (US)
Pages (from-to)554-560
Number of pages7
JournalJournal of Heart and Lung Transplantation
Volume27
Issue number5
DOIs
StatePublished - May 2008

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Dependovirus
Genes
Perfusion
Isogeneic Transplantation
Heterotopic Transplantation
Viral Genes
Viral Genome
Heart Transplantation
Immunoenzyme Techniques
Genetic Therapy
Histology
Transplantation
Serogroup
Viruses
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Surgery
  • Transplantation

Cite this

Efficient and Durable Gene Transfer to Transplanted Heart Using Adeno-associated Virus 9 Vector. / Miyagi, Naoto; Rao, Vinay P.; Ricci, Davide; Du, Zeji; Byrne, Guerard W.; Bailey, Kent R; Nakai, Hiroyuki; Russell, Stephen J; McGregor, Christopher G A.

In: Journal of Heart and Lung Transplantation, Vol. 27, No. 5, 05.2008, p. 554-560.

Research output: Contribution to journalArticle

Miyagi, Naoto ; Rao, Vinay P. ; Ricci, Davide ; Du, Zeji ; Byrne, Guerard W. ; Bailey, Kent R ; Nakai, Hiroyuki ; Russell, Stephen J ; McGregor, Christopher G A. / Efficient and Durable Gene Transfer to Transplanted Heart Using Adeno-associated Virus 9 Vector. In: Journal of Heart and Lung Transplantation. 2008 ; Vol. 27, No. 5. pp. 554-560.
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