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.


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.
Duncan
V E
VE
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville 32603, USA.
Ajmani
P S
PS
Hughes
J A
JA
D001692:Biological Transport; D018274:Electroporation; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D009447:Neuroblastoma; D009838:Oligodeoxyribonucleotides / Q000493:pharmacokinetics* / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000493:pharmacokinetics* / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics; D013873:Thionucleotides; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D009838:Oligodeoxyribonucleotides; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D019098:Telomerase