Adeno-associated virus is one of an emerging group of viral vectors that may provide renewed enthusiasm for viral delivery of therapeutic products to treat joint disease. Adenovirus and retrovirus, while providing advantages in either transduction efficiency or transgene integration, both have either production, safety, or gene persistence draw-backs that limit their application in cartilage repair and arthritis treatment. This proposal will allow the candidate to use contemporary techniques in AAV vector construction to generate an AAV-IGF-I vector, to test the composite for effective integration and prolonged expression of the growth factor gene coding sequence, and finally to document the stimulatory effects it has on chondrocyte and synoviocyte metabolism and proliferation. The investigators will use contemporary triple-plasmid methods for propagation, and the examination of gene persistence in target cells will use real-time PCR and microarray techniques. Effector cell responses will be gauged by radioimmunological assay, and the protein up-regulation will be assessed by dye-binding and immunocytochemical techniques. The sponsor has extensive experience in vector development, and his laboratory and colleagues are leaders in AAV research and production. The candidate will participate in the production of vectors, integrate his own molecular biology background into transgene construction, and develop reliable vector cloning and production proficiency during this 12-month study.
| Nixon, Alan J; Goodrich, Laurie R; Scimeca, Michael S et al. (2007) Gene therapy in musculoskeletal repair. Ann N Y Acad Sci 1117:310-27 |
| Trippel, S B; Ghivizzani, S C; Nixon, A J (2004) Gene-based approaches for the repair of articular cartilage. Gene Ther 11:351-9 |
