Robbins P D, Evans C H, Chernajovsky Y
Department of Molecular Genetics and Biochemistry, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Gene Ther. 2003 May;10(10):902-11. doi: 10.1038/sj.gt.3302040.
Rheumatoid arthritis is an autoimmune disease with intra-articular inflammation and synovial hyperplasia that results in progressive degradation of cartilage and bone, in severe cases it causes systemic complications. Recently, biological agents that suppress the activities of proinflammatory cytokines have shown efficacy as antiarthritic drugs, but require frequent administration. Thus, gene transfer approaches are being developed as an alternative approach for targeted, more efficient and sustained delivery of inhibitors of inflammatory cytokines as well as other therapeutic agents. Indeed, the efficacy of gene transfer for the treatment of arthritis has been demonstrated in mouse, rat, rabbit, and horse models of disease whereas the feasibility of the approach has been demonstrated in Phase I clinical trials. In this review, the current status of both preclinical and clinical arthritis gene therapy is presented. In addition, the advantages and disadvantages of different types of vectors, target cells and therapeutic genes being developed for the treatment of arthritis are summarized. Finally, the future directions of the rapidly developed field of arthritis gene therapy are outlined.
类风湿性关节炎是一种自身免疫性疾病,伴有关节内炎症和滑膜增生,会导致软骨和骨骼的逐渐退化,严重时会引发全身并发症。最近,抑制促炎细胞因子活性的生物制剂已显示出作为抗关节炎药物的疗效,但需要频繁给药。因此,基因转移方法正在被开发,作为一种替代方法,用于靶向、更有效和持续地递送炎性细胞因子抑制剂以及其他治疗剂。事实上,基因转移治疗关节炎的疗效已在小鼠、大鼠、兔子和马的疾病模型中得到证实,而该方法的可行性已在I期临床试验中得到证实。在这篇综述中,介绍了临床前和临床关节炎基因治疗的现状。此外,总结了为治疗关节炎而开发的不同类型载体、靶细胞和治疗基因的优缺点。最后,概述了快速发展的关节炎基因治疗领域的未来方向。