Cellular delivery is a major obstacle for oligodeoxynucleotide inhibition of telomerase activity.

BACKGROUND: The ribonucleoprotein enzyme, telomerase, uses RNA as a template to add a hexanucleotide to ends of replicating chromosomes resulting in stabilization of the telomere. Telomerase activity is observed in over 85% of human primary malignancies, suggesting that it may be a new marker of cancer and raising the possibility that antitelomerase therapy may provide a new generation of cancer therapeutics. MATERIALS AND METHODS: In this study, we evaluated phosphorothioate (PS) oligonucleotide (ODNs) inhibition of telomerase activity in intact cells and cell lysates in the SKnSH (neuroblastoma) cell line. RESULTS: The ODNs were effective at inhibiting telomerase activity in cell lysate but demonstrated little effect when intact cells were used. CONCLUSIONS: This study demonstrates that cellular transport may be a limiting factor with therapeutic approaches using antisense ODNs.