肿瘤基因治疗新战略.Ribozyme抑制端粒酶活性研究

Telomerase has a tight relationship with tumor growth, so telomerase inhibitor is a good anti-cancer drug with broad usage.We desighed and synthesized two ribozymes targeted to the 2239 site and the 5'-end of the human telomerase transcriptase(hTERT) mRNA, then cloned it to the in vitro transcriptional and eukaryotic expressing plasmids.The ribozyme targeted to the 2239 site of hTERT mRNA can cleavage 65% template RNA,inhibit the telomerase activity of HeLa cell and 7402 cell, and enlongate the double time of cell growth,but can not induce the cell apoptosis.The ribozyme targeted to the 5'-end of hTERT mRNA can inhibit the telomerase activity to a very low grade, as a stronger inhibitor than another ribozyme (teloRZ) targeted to telomerase template RNA. So it's a telomerase inhibitor with a broad prospect to be used in cancer gene therapy.

人端粒酶激活是体细胞恶性转化的关键步骤。抑制端粒酶活性即可抑制肿瘤的发生和发展。端粒酶逆转录酶蛋白（hTERI）是其催化活性核心部分。一旦受损，该酶即丧失功能活性。耍颐枪顾己铣杉钢痔匾靐TERT的Ribozyme，以切割破坏hTERT结构，从而抑制端粒酶活裕掌戎琢鱿赴搿俺绦蛐运劳觥薄？僖惶蹙哂芯薮蠓⒄骨绷Φ闹琢龌蛑瘟菩峦揪丁