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, Steven J Russell, Christopher G.A. McGregor

Research output: Contribution to journalArticlepeer-review

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
Externally publishedYes

Keywords

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

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