Pharmacokinetic Properties of Phosphorothioates in Animals — Absorption, Distribution, Metabolism and Elimination
Antisense Research and ApplicationHandbook of Experimental Pharmacology(1998)
Abstract
Antisense oligonucleotides can hybridise with target mRNA and cause protein-specific translation arrest (Zamecnik and Stevenson 1978; Helene and Toulme 1990). This “antisense concept” is a simple, generic and rational approach to drug discovery which has stimulated considerable
interest in the potential of oligonucleotides as therapeutic agents (Crooke 1995). Indeed, there are now many examples where antisense oligonucleotides have demonstrated efficacy against disease-relevant
targets, notably for tumour (Higgins et al. 1993; Monia et al. 1996; Dean et al. 1996) and viral (Agrawal 1992; Wagner and Flanagan 1997) indications. The rapid emergence of this class of compounds has placed new demands on the preclinical profiling of therapeutic
candidates, particularly with respect to their in vivo behaviour.
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