Survivin mRNA antagonists using locked nucleic acid, potential for molecular cancer therapy.
We have investigated the effects of different locked nucleic acid modified antisense mRNA antagonists against Survivin in a prostate cancer model. These mRNA antagonists were found to be potent inhibitors of Survivin expression at low nanomolar concentrations. Additionally there was a pronounced synergistic effect when combining the mRNA antagonists against Survivin with the chemotherapeutic Taxol. This effect was demonstrated at concentrations of antagonists far lower than any previously demonstrated, indicating the high potential of locked nucleic acid for therapeutic use. Further characterisations in vivo are ongoing.
Fisker
Niels
N
Santaris Pharma A/S, Boege Allé 3, DK-2970 Hoersholm, Denmark. NFN@santaris.com
Westergaard
Majken
M
Hansen
Henrik Frydenlund
HF
Hansen
Jens Bo
JB
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000037:antagonists & inhibitors*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D009841:Oligonucleotides / Q000737:chemistry*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D016372:RNA, Antisense / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D012333:RNA, Messenger / Q000037:antagonists & inhibitors*; D000077022:Survivin
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009841:Oligonucleotides; D016372:RNA, Antisense; D012333:RNA, Messenger; D000077022:Survivin; C477371:locked nucleic acid