Recombinant adeno-associated virus vector for gene transfer to the transplanted rat heart

Johannes M. Schirmer, Naoto Miyagi, Vinay P. Rao, Davide Ricci, Mark J. Federspiel, Robert M. Kotin, Stephen J. Russell, Christopher G.A. McGregor

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Efficient durable viral vector transduction of the transplanted heart remains elusive. This study assesses the potential of recombinant adeno-associated virus (rAAV) mediated gene delivery to the transplanted rat heart. rAAV serotype 1, 2 and 5 vectors encoding the green fluorescent protein (GFP) gene (1 × 1011 viral particles/ml) were diluted in cold University of Wisconsin solution and circulated through the coronary vasculature of the donor organs for 30 min before syngeneic rat heterotopic heart transplantation was performed. Study 1: animals (n = 5 each serotype) were killed at 21 days post-transplant to evaluate the efficiency of GFP transduction using RT-PCR and expression by fluorescence microscopy. Study 2: using rAAV-1, animals (n = 5 each group) were killed at 7, 21 and 84 days to evaluate the durability of GFP expression. The maximum cardiac GFP expression at 21 days was observed in rAAV-1. GFP expression by rAAV-1 was detectable at 7 days, improved at 21 days, and was still evident at 84 days. This study demonstrates cardiac rAAV gene transduction with a cold perfusion preservation system of the donor heart. These data show that AAV-1 is superior to AAV-2 and AAV-5 for this purpose and that durable expression is achievable.

Original languageEnglish (US)
Pages (from-to)550-557
Number of pages8
JournalTransplant International
Volume20
Issue number6
DOIs
StatePublished - Jun 2007

Keywords

  • Adeno-associated virus vector
  • Cold perfusion system
  • Gene therapy
  • Heart transplantation
  • Rat

ASJC Scopus subject areas

  • Transplantation

Fingerprint Dive into the research topics of 'Recombinant adeno-associated virus vector for gene transfer to the transplanted rat heart'. Together they form a unique fingerprint.

  • Cite this