PHARMACOLOGY AND TOXICOLOGY OF PHOSPHOROTHIOATE OLIGONUCLEOTIDES IN THE MOUSE, RAT, MONKEY AND MAN

Phosphorothioate oligonucleotides (PS-ODN) designed to temporarily mod ulate selected gene expression have made the journey from bench top to bedside in a remarkably short period of time. A PS-ODN with sequence complementary to the p53 mRNA was administered to mice (4 mg/kg subcut aneously), rats (3-300 mg/kg intravenously), monkeys (intravenous infu sions for up to 15 days) and humans (up to 0.25 mg/kg/h intravenous in fusions for 10 days). These studies demonstrate the PS-ODN provides fe asible pharmacokinetic parameters and minimal toxicity.