1094. Self-Complementary Vectors Significantly Enhance AAV-Mediated Gene Transfer to Joint Tissues

Gene delivery approaches have been proposed as a means to improve treatment of the arthritides. By delivering cDNAs encoding anti-arthritic proteins to the cells in the synovial lining, the gene products may be expressed and secreted locally into the joint space. Vectors based on AAV offer advantages that would favor their use as a vehicles for direct, intra-articular gene transfer; however, reports of the effectiveness of this vector have been widely variable. Much of this inconsistency may be due to limitations in synovial lining/ joint capsular cells to initiate second strand DNA synthesis of the recombinant virus. To address this hypothesis we evaluated self-complementary (sc; double-stranded) AAV serotype 2 vectors for their capacity to deliver and enable expression of exogenous cDNAs in synovial fibroblasts in vitro, and in the joints of rabbits in vivo.