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- Title
Recombinant adeno-associated virus vector for gene transfer to the transplanted rat heart.
- Authors
Schirmer, Johannes M.; Miyagi, Naoto; Rao, Vinay P.; Ricci, Davide; Federspiel, Mark J.; Kotin, Robert M.; Russell, Stephen J.; McGregor, Christopher G. A.
- 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.
- Subjects
UNITED States; TRANSPLANTATION of organs, tissues, etc.; HEART transplantation; BLOOD vessels; BACTERIOPHAGES; GREEN fluorescent protein
- Publication
Transplant International, 2007, Vol 20, Issue 6, p550
- ISSN
0934-0874
- Publication type
Article
- DOI
10.1111/j.1432-2277.2007.00479.x