ANTISENSE TARGETED TO C-MYC MRNA INHIBITS SMOOTH MUSCLE CELL PROLIFERATION

针对 C-MYC mRNA 的反义蛋白抑制平滑肌细胞增殖

• 批准号: 3858155
• 负责人: S BIRO
• 金额: --
• 依托单位: NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3858155
• 关键词: antisense nucleic acid; genetic translation; growth inhibitors; human tissue; hybrid cells; intraluminal angioplasty; messenger RNA; myocardial ischemia /hypoxia; smooth muscle

Percutaneous transluminal angioplasty (PTCA) has been an important therapy in ischemic heart disease. However, its limitation is restenosis which occurs in 25-55% of patients after PTCA within 6 months. The main cause of restenosis is proliferation of smooth muscle cells. If we can prevent the proliferation of smooth muscle cells, PTCA will be a more effective therapy. We have been trying to inhibit smooth muscle cell proliferation. We are employing antisense strategy to inhibit the proliferation of smooth muscle cells. Antisense oligodeoxynucleotides are complementary to normal mRNA. They hybridize to the mRNA, and thereby inhibit the translation of mRNA so that the protein encoded by the specific mRNA targeted is not expressed. We hypothesized that if we could inhibit expression of factors that are necessary for cell proliferation, we could actually inhibit proliferation. This year we found that anti-sense oligodeoxynucleotide complementary to c-myc mRNA did inhibit the proliferation of smooth muscle cells in vitro.

经皮腔内血管成形术（PTCA）已成为一种重要的治疗方法 在缺血性心脏病中。 然而，其局限性是再狭窄， 25-55% 的患者在 PTCA 术后 6 个月内发生。 主要原因 再狭窄的原因是平滑肌细胞的增殖。 如果我们能阻止 平滑肌细胞的增殖，PTCA将是更有效的 治疗。 我们一直在努力抑制平滑肌细胞的增殖。 我们采用反义策略来抑制平滑肌细胞的增殖 肌肉细胞。 反义寡脱氧核苷酸与正常寡核苷酸互补 mRNA。 它们与 mRNA 杂交，从而抑制 mRNA 使得特定 mRNA 所编码的蛋白质不被靶向 表示。 我们假设如果我们能够抑制因子的表达 这是细胞增殖所必需的，我们实际上可以抑制 增殖。 今年我们发现反义寡聚脱氧核苷酸 与c-myc mRNA互补确实抑制平滑肌的增殖 体外细胞。