874. Prolonged Adenovirus and Adeno-Associated Virus-Mediated Gene Delivery to Rabbit Iliac Arteries Using Gene-Eluting Stents: A Direct Comparison

Top of pageAbstract Introduction: Gene eluting stents are now being evaluated in animals as an alternative approach to inhibiting in stent restenosis. AAV and particularly adenovirus are commonly used for gene transfer applications. However, it is unknown whether these vectors can be eluted from a stent over a prolonged period. We tested the hypothesis that these vectors can achieve a prolonged and localized gene delivery to vessel wall using stents as delivery platform. Methods: Ad|[beta]|Gal and AAV2|[beta]|Gal at a concentration of 5 |[times]| 109 pfu and 5.3 |[times]| 109 drp respectively were used to coat BiodivYsio Hi Matrix stents. Gene transfer was assessed at five time points (3, 7, 14, 21, 28 days) using X-gal staining. After balloon injury, 3.0/11 mm stents were deployed in the external iliac arteries of NZW rabbits. 21 stents were used in the adenovirus group and 23 stents were used in the AAV group. 8 PC coated stents were used as controls. RT-PCR was used to assess distal spread of virus in multiple organs (n=6). Results: Expression of LacZ was demonstrated with both vectors at all time points. In the adenovirus group mean percentage of cells expressing transgene at 3 days was 5.15% which increased gradually to a mean expression of 9.85% at 28 days (p>0.005). Expression was localized to medial cells at 3 day, but it was predominantly seen in the neointimal cells at 28 days. In the AAV group 3 day expression was 8.45% which gradually decreased to 1.73% at 28day (p<0.005). Gene transfer was also confirmed in both groups on histological sections. No systemic dissemination of virus was seen in any group. Conclusion: Adenovirus and AAV2-coated stents can be used to deliver genes for up to 28 days. Expression was seen in the medial and in neointimal cells. These vectors can be used to target the blood vessel wall in order to reduce the incidence of in stent restenosis.