Intra-articular delivery of an AAV-anti-TNF-α vector alleviates the progress of arthritis in a RA mouse model

Rheumatoid Arthritis is a chronic, inflammatory autoimmune disease marked by joint destruction and functional impairment. Tumor Necrosis Factor (TNF) plays a critical role in RA pathogenesis. While TNF-targeting drugs are clinically effective, their need for frequent and long-term administration often results in poor patient adherence and suboptimal outcomes. This study developed a gene therapy approach using engineered adeno-associated virus (AAV) vectors to deliver an anti-TNF agent directly into the joint cavity of RA animal models. Animals receiving this therapy demonstrated sustained improvement in clinical scores, inflammatory markers, and joint tissue health. Immunofluorescence staining revealed that AAV vectors could transduce various cell types, including T cells, type A synoviocytes, and dendritic cells. Experimental results indicated that a single administration of this gene therapy provided long-term efficacy. The finding suggest that AAV-mediated anti-TNF gene therapy is highly effective in RA animal models, offering prolonged relief from clinical symptoms and reducing inflammatory damage. This innovative approach presents a promising potential for gene therapy with significant clinical prospects.