Adeno-associated virus-mediated gene transfer in a rabbit vein graft model

BACKGROUND: Stenoses of venous grafts represent a major limitation in coronary artery bypass surgery. The use of viral vectors to facilitate over-expression of factors within the graft to promote long-term patency is a promising new therapeutic concept. One of the viral vector systems is the adeno-associated virus (AAV); a non-pathogenic single stranded DNA virus, which elicits only low immunological responses.

METHODS AND RESULTS: Recombinant AAV vector coding for beta-galactosidase was produced and transferred ex vivo using intraluminal application to previously harvested rabbit internal jugular vein grafts (n = 8). The 30 min after application, an end-to-end anastomosis of each graft as a bypass to the carotid artery was performed in a previously established rabbit bypass model. X-Gal-staining of the grafts was performed after killing the animals to quantify gene expression. AAV transduction was successful in 100% of the grafts. After 30 days, beta-galactosidase gene expression could be assessed in the medial layer of the graft. Furthermore, no signs of inflammation could be detected.

CONCLUSIONS: These findings suggest that recombinant AAV vectors are an alternative to the widely used adenoviral based vectors. These data support the further use of AAV vectors to overcome intimal hyperplasia after vein graft coronary artery bypass surgery.