Telomerase RNA inhibition using antisense oligonucleotide against human telomerase RNA linked to a 2',5'-oligoadenylate.
Telomerase, a ribonucleoprotein enzyme, is detected in the vast majority of cancers, including malignant gliomas, but not in most normal somatic cells. To inhibit telomerase function effectively, we have adopted the 2',5'-oligoadenylate (2-5A) antisense system. 2-5A is a mediator of one pathway of interferon actions by activating RNase L, resulting in single-stranded RNA cleavage. By linking 2-5A to an antisense oligonucleotide, RNase L degrades the targeted RNA specifically and effectively. Therefore, we have synthesized the antisense oligonucleotide against human telomerase RNA component (hTR) linked to 2-5A (2-5A-anti-hTR) and have demonstrated its antitumor effect on telomerase-positive cancer cells in vitro and in vivo.
Kondo
Yasuko
Y
Department of Neurosurgery, Anderson Cancer Center, Houston, TX, USA.
Kondo
Seiji
S
D000227:Adenine Nucleotides / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008967:Molecular Biology / Q000379:methods*; D021141:Nucleic Acid Amplification Techniques; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D009843:Oligoribonucleotides / Q000378:metabolism*; D012313:RNA / Q000037:antagonists & inhibitors* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics*; D016615:Telomere / Q000378:metabolism
D000227:Adenine Nucleotides; D016376:Oligonucleotides, Antisense; D009843:Oligoribonucleotides; C422952:telomerase RNA; C023505:2',5'-oligoadenylate; D012313:RNA; D019098:Telomerase