Gene therapy for arthritis: principles and clinical practice.
Gene therapy for arthritis: principles and clinical practice.
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关节炎的基因治疗：原理和临床实践。
DOI：
10.1042/bst0250533
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发表时间：
1997
影响因子：
3.9
通讯作者：
Evans,CH
中科院分区：
文献类型：
--
作者：
Kang,R;Ghivizzani,SC;Herndon,JH;Robbins,PD;Evans,CH
关节炎是一种常见的致残性疾病，目前还没有治愈方法，也很少有有效的治疗方法。然而，最近对类风湿性关节炎（RA）和骨关节炎（OA）（关节炎的两种最常见形式）的生物学的研究已经鉴定了许多具有有希望的抗关节炎、免疫调节或软骨保护性质的潜在抗关节炎蛋白。这些蛋白质中的一些已经在关节炎的动物模型中进行了评估，结果令人鼓舞。这种介质的临床应用由于缺乏将其递送给关节炎患者的合适手段而受到很大阻碍。蛋白质的口服给药是无效的，并且通过注射递送是低效的，因为它们被快速清除。为了规避这些限制，我们建议，与其递送治疗性蛋白质本身，不如递送编码它们的基因。在这个意义上，我们提出基因转移作为分泌的抗关节炎蛋白的生物药物递送系统[1 -41]。虽然这一概念可以扩展到包括递送其他基因产物，如在细胞内起作用的反义RNA或转录因子，但使用编码分泌蛋白的基因具有最大的早期成功机会，因为它可以以离体方式使用，并且不需要不合理的高转导效率。在这方面，最紧迫的问题是
Arthritic diseases are common crippling conditions for which there are no cures and few useful treatments. Nevertheless recent research into the biology of rheumatoid arthritis (RA) and osteoarthritis (OA), the two most common forms of arthritis, has identified a number of potentially anti-arthritic proteins with promising antiinflammatory, immunomodulatory or chondroprotective properties. A number of these proteins have been evaluated in animal models of arthritis, with encouraging results. Clinical application of such mediators is greatly hindered by the lack of a suitable means for delivering them to patients with arthritis. Oral administration of proteins is ineffective, and delivery by injection is inefficient because of the rapidity with which they are cleared. To circumvent these limitations, we have suggested that instead of delivering the therapeutic proteins themselves, it would be better to deliver the genes that encode them. In this sense, we are proposing gene transfer as a biological drugdelivery system for secreted anti-arthritic proteins [l-41. Although this concept can be extended to include the delivery of other gene products, such as anti-sense RNA or transcription factors, which act intracellularly, the use of genes encoding secreted proteins stands the greatest chance of early success as it can be used in an ex vivo fashion and does not require unreasonably high transduction efficiencies. In this context, the most immediate questions to be