Pharmacodynamics And Biodistribution Of Recombinant Adeno-associated Virus/Type Tumor Necrosis Factor Receptor: IgG₁ Fc In Rat Rheumatoid Arthritis Model

Rheumatoid arthritis (RA) is a chronic systemic autoimmune inflammatory disease with unknown etiology. It is generally accepted that cytokines network plays an important role in RA pathological process. Tumor necrosis factor-alpha (TNFα) is one of the most important inflammation factors, which is a multifunctional cytokine secreted by macrophage or monocytes with activities closely correlating with many autoimmune disease including RA. Clinical symptomatic relief of RA could be achieved through TNFα receptor binding blockage by biopharmaceutical products in recent years. All of these products are protein preparations, among which Enbrel (soluble human tumor necrosis factor receptor-IgG₁ Fc, i.e. TNFR:Fc) is the most successful. But these proteins are systematic administration with high cost and short dosing interval. These drawbacks limit its use. However, comparatively higher level of therapeutic protein raised by local administration, long term gene expression in vivo, and relative long dosing interval are all predominance of gene therapy. Gene therapy has being become one of the most promising therapeutic tools for RA.With TNFα being target gene, recombinant adeno-associated virus/ type II tumor necrosis factor receptor-IgG₁ Fc (rAAV/TNFR:Fc) is a gene product which is recently developed and expected to treat RA. TNFR:Fc fusion gene was constructed by...