Gene therapy for spine damage repair Sponsor: AOSpine, Gavos, Switzerland

Gene therapy has emerged as a very promising approach to enhance bone repair because the potential for sustained production of osteogenic factors may enable osteoprogenitor cells to respond in a more robust fashion. In this project we propose to insert in specific vectors those genes important for bone growth in patients with congenital and acquired diseases of spine. To deliver specific genes into cells, viral (transduction) and non-viral (transfection) vectors can be used. Several properties make the simian virus 40 (SV40), a polyomavirus with a double-stranded circular DNA of approximately 5k bp, a good candidate to be used as a vector for gene therapy approaches. Several genes are good candidates for our aim: bone morphogenetic proteins (BMPs), transforming growth factor-beta (TGF-beta), insulin-like growth factors (IGFs), fibroblast growth factors (FGFs), LIM mineralization protein-1 (LMP-1), vascular endothelial growth factor (VEGF) and the constitutively active form of the activin receptor-like kinase-2 (caAlk2). In this way, we can generate recombinant SV40 viruses (rSV40), with specific properties such as replication deficient, nononcogenic and nonimmunogenic. The efficacy of these recombinant SV40 viruses can be studied both in cell cultures and in animal models.