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Pharmacology and toxicology of phosphorothioate oligonucleotides in the mouse, rat, monkey and man
P L Iversen1, B L Copple, H K Tewary
1Department of Pharmacology, Eppley Institute for Cancer Research, University of Nebraska Medical Center, Omaha 68198-6260, USA.
Toxicology Letters
|December 1, 1995
Abstract:
Phosphorothioate oligonucleotides (PS-ODN) designed to temporarily modulate selected gene expression have made the journey from bench top to beside in a remarkably short period of time. A PS-ODN with sequence complementary to the p53 mRNA was administered to mice (4 mg/kg subcutaneously), rats (3-300 mg/kg intravenously), monkeys (intravenous infusions for up to 15 days) and humans (up to 0.25 mg/kg/h intravenous infusions for 10 days). These studies demonstrate the PS-ODN provides feasible pharmacokinetic parameters and minimal toxicity.