ANIMAL-MODELS OF ANTISENSE OLIGONUCLEOTIDES - LESSONS FOR USE IN HUMANS

The ability of oligonucleotides to inhibit genetic expression in a seq uence-specific manner has been well documented. Because of their poten tial for exquisite specificity, oligonucleotides have been proposed as therapeutic agents for a variety of human diseases, including cancers , microbial infections and autoimmune disorders. Approximately 16 clin ical trials are currently in progress, However, relatively little is k nown about the in vivo behaviour of oligonucleotides. Extrapolations f rom in vitro studies to predict in vivo pharmacokinetics and effects i n humans might be difficult and inappropriate. Animal models still rem ain an essential tool in the development of oligonucleotides as effici ent drugs in humans.