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.