类风湿性关节炎（RA）是一种慢性炎症性自身免疫性疾病，以关节破坏和功能障碍为特征。肿瘤坏死因子（TNF）在 RA 发病机制中发挥着关键作用。尽管 TNF 靶向药物在临床上有效，但需要频繁和长期给药，通常会导致患者依从性差和结果不佳。这项研究开发了一种基因治疗方法，使用工程腺相关病毒 (AAV) 载体将抗 TNF 药物直接递送到 RA 动物模型的关节腔中。接受这种治疗的动物表现出临床评分、炎症标志物和关节组织健康的持续改善。免疫荧光染色显示AAV载体可以转导多种细胞类型，包括T细胞、A型滑膜细胞和树突状细胞。我们的结果表明，这种基因疗法的单次给药可提供长期疗效。这表明 AAV 介导的抗 TNF 基因疗法可以长期缓解 RA 小鼠模型的临床症状并减少炎症损伤。这种创新方法提供了一种有前景的新疗法，对于治疗 RA 患者具有重要的临床前景。

Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease marked by joint destruction and functional impairment. Tumor necrosis factor (TNF) plays a critical role in RA pathogenesis. Although 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. Our results indicate that a single administration of this gene therapy provided long-term efficacy. This suggests that AAV-mediated anti-TNF gene therapy can offer prolonged relief from clinical symptoms and reduce inflammatory damage in a mouse model of RA. This innovative approach presents a promising new therapy with significant clinical prospects to treat patients with RA.