Knockdown of telomerase RNA using hammerhead ribozymes and RNA interference.
More than 85% of human cancers and over 70% of immortalized human cell lines have highly elevated telomerase activity. In contrast, telomerase activity is down-regulated in most human adult somatic cells, except stem cells and germ cells. These results are consistent with telomerase conferring a selective advantage for continued proliferation of malignant cells and present a unique target for cancer gene therapy. In line with this view, our recent results suggest that knockdown of telomerase RNA in human or in mouse cancer cells by ribozyme or RNA interference (RNAi) diminishes telomerase activity and inhibits cancer cell growth both in vitro and in vivo. Such telomerase inhibiting agents represent a promising novel cancer therapeutic strategy. In this chapter, we will discuss the knockdown of telomerase RNA by hammerhead ribozyme and RNAi. Both techniques are mediated by sequence-specific recognition of target RNA by a guide RNA molecule, which then results in the nucleolytic degradation of the RNA target.
Li
Shang
S
UCSF Comprehensive Cancer Center, San Francisco, CA, USA.
Nosrati
Mehdi
M
Kashani-Sabet
Mohammed
M
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D051379:Mice; D008967:Molecular Biology / Q000379:methods*; D008969:Molecular Sequence Data; D012313:RNA / Q000037:antagonists & inhibitors* / Q000235:genetics*; D034622:RNA Interference; D016337:RNA, Catalytic / Q000235:genetics* / Q000494:pharmacology*; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics*
D016337:RNA, Catalytic; D034741:RNA, Small Interfering; C427204:hammerhead ribozyme; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase