Kitajima I, Hanyu N, Kawahara K, Soejima Y, Kubo T, Yamada R, Kaneda Y, Maruyama I
Kagoshima University, Kagoshima City, Japan.
Arthritis Rheum. 1997 Dec;40(12):2118-27. doi: 10.1002/art.1780401205.
To develop gene therapy for patients with human T cell leukemia virus type I (HTLV-I)-associated arthropathy (HAAP), we investigated the effects of ribozyme-mediated cleavage of HTLV-I tax/rex messenger RNA (mRNA) on synovial overgrowth.
We introduced 2 hammerhead ribozymes targeted against HTLV-I tax/rex mRNA into synovial cells obtained from patients with HAAP and from patients with HTLV-I-negative rheumatoid arthritis (RA) and examined the ribozyme-mediated ablation of Tax expression. Using standard methods, we also determined the cells' ability to stop proliferating and to undergo apoptosis.
The ribozymes successfully cleaved tax/rex mRNA in HAAP patient synoviocytes. Both tax mRNA expression and Tax protein synthesis were inhibited significantly, resulting in inhibition of synovial cell growth and induction of apoptosis. In contrast, synovial cells from RA patients were not affected.
In vitro results suggest that ribozyme-mediated gene therapy can inhibit the growth of HTLV-I-infected synovial cells, which is maintained by Tax protein, in HTLV-I-related diseases including HAAP.
为开发针对I型人类T细胞白血病病毒（HTLV-I）相关关节病（HAAP）患者的基因疗法，我们研究了核酶介导的HTLV-I tax/rex信使核糖核酸（mRNA）切割对滑膜过度生长的影响。
我们将2种靶向HTLV-I tax/rex mRNA的锤头状核酶导入从HAAP患者和HTLV-I阴性类风湿关节炎（RA）患者获取的滑膜细胞中，并检测核酶介导的Tax表达消除情况。我们还使用标准方法确定了细胞停止增殖和发生凋亡的能力。
核酶成功切割了HAAP患者滑膜细胞中的tax/rex mRNA。tax mRNA表达和Tax蛋白合成均受到显著抑制，导致滑膜细胞生长受到抑制并诱导凋亡。相比之下，RA患者的滑膜细胞未受影响。
体外研究结果表明，在包括HAAP在内的HTLV-I相关疾病中，核酶介导的基因疗法可抑制由Tax蛋白维持的HTLV-I感染滑膜细胞的生长。
