Evans C H, Robbins P D
University of Pittsburgh School of Medicine, Department of Orthopaedic Surgery, PA 15213, USA.
Intern Med. 1999 Mar;38(3):233-9. doi: 10.2169/internalmedicine.38.233.
Genes encoding anti-arthritic products can be transferred to intra-or extraarticular sites where their expression suppresses various aspects of the pathophysiology of arthritis. A variety of viral and non-viral vectors can be used for the in vivo or ex vivo delivery of such genes. Promising pre-clinical data have resulted from the application of these strategies in several animal models of disease. Genes showing efficacy in this way include these encoding interleukin (IL) -1Ra, IL-1sR, TNFsR, transforming growth factor beta (TGF-beta), IL-13, Fas L, IL- 10 and vIL-10. Two human arthritis gene therapy protocols are underway in the USA and Germany. Both studies involve the ex vivo transfer of an IL-1Ra cDNA to the metacarpophalangeal joints of patients with rheumatoid arthritis. Progress in developing gene treatments for arthritis has been rapid, and permits optimism about their ability eventually to improve the treatment of this group of diseases.
编码抗关节炎产物的基因可被转移至关节内或关节外部位,在这些部位其表达可抑制关节炎病理生理学的各个方面。多种病毒和非病毒载体可用于此类基因的体内或体外递送。在几种疾病动物模型中应用这些策略已产生了有前景的临床前数据。以这种方式显示出疗效的基因包括编码白细胞介素(IL)-1Ra、IL-1sR、肿瘤坏死因子受体(TNFsR)、转化生长因子β(TGF-β)、IL-13、Fas L、IL-10和痘病毒IL-10的基因。美国和德国正在进行两项人类关节炎基因治疗方案。两项研究均涉及将IL-1Ra cDNA体外转移至类风湿性关节炎患者的掌指关节。关节炎基因治疗的进展迅速,让人对其最终改善这类疾病治疗的能力感到乐观。