Inhibition of human telomerase by oligonucleotide chimeras, composed of an antisense moiety and a chemically modified homo-oligonucleotide

Most tumor cells attain their immortality by reactivating telomerase. We report here the telomerase inhibitory potential of chimeric oligonucleotides composed of a 13mer antisense sequence targeting the telomerase RNA template region and a (s4dU)n moiety at its 3′ or 5′-end. The increase of the thiolated chain length enhances the telomerase inhibitory potential, but decreases specificity, indicated by HIV reverse transcriptase inhibition. Chimeras with 5′ (s4dU)ns were more potent inhibitors than the antisense alone or the 3′ modified ones. Cy5-labeled (s4dU)4AS and (s4dU)8AS proved the internalization of the oligonucleotides, raising the possibility to be tested as cellular anti-telomerase agents.