Tomita Tetsuya, Hashimoto Hideo, Yoshikawa Hideki
Falk Cardiovascular Research Center, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
Curr Drug Targets. 2003 Nov;4(8):609-12. doi: 10.2174/1389450033490777.
Recent progress in molecular biology has provided application of gene transfer methods in arthritis. Two clinical trails using ex vivo retrovirus mediated delivery of interleukin -1 receptor antagonist gene for rheumatoid arthritis has begun in USA and Germany. However, there are still many issues to be elucidated; one is the development of gene delivery system, and the other is the selection of therapeutic gene. Arthritis is nonlethal disease, and safety is one of the important issues. Currently viral mediated vectors are major even in clinical trials however, non viral efficient gene transfer system should be developed in future. Recently the application of DNA technologies, such as antisense oligonucleotide (ODN) strategies to regulate the transcription of disease-related genes in vivo, has significant therapeutic potential. Transfection of cis-clement double-stranded oligonucleotides (decoy ODN) for nuclear factor kappaB binding site has been reported as a new powerful tool in arthritis. The concept of regulation the disease related gene expression at the level of transcriptional factor may be more therapeutic effects compared with monotherapy in arthritis.
分子生物学的最新进展已将基因转移方法应用于关节炎治疗。美国和德国已开始两项利用体外逆转录病毒介导递送白细胞介素-1受体拮抗剂基因治疗类风湿性关节炎的临床试验。然而，仍有许多问题有待阐明；一个是基因递送系统的开发，另一个是治疗性基因的选择。关节炎并非致命疾病，安全性是重要问题之一。目前，即使在临床试验中病毒介导的载体仍是主要手段，不过未来应开发非病毒高效基因转移系统。近来，DNA技术的应用，如反义寡核苷酸（ODN）策略在体内调节疾病相关基因的转录，具有显著的治疗潜力。针对核因子κB结合位点转染顺式作用双链寡核苷酸（诱饵ODN）已被报道为关节炎治疗中的一种新的有力工具。与关节炎单一疗法相比，在转录因子水平调节疾病相关基因表达的概念可能具有更大的治疗效果。
