Preclinical Profiling of Modified Oligonucleotides: Anticoagulation and Pharmacokinetic Properties

Abstract

Abstract Backbone, sugar and pendant-group modifications were shown to influence the anticoagulant properties of a 20-mer oligonucleotide in human plasma in vitro. The pharmacokinetics, tissue-distribution and metabolism of a chimeric oligonucleotide (CGP 69845A), which had reduced anticoagulation properties, were compared with the analogous phosphorothioate oligodeoxynucleotide (CGP 69846A) in a tumour-bearing mouse model.