Animal models of antisense oligonucleotides: lessons for use in humans.

The ability of oligonucleotides to inhibit genetic expression in a sequence-specific manner has been well documented. Because of their potential 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 clinical trials are currently in progress. However, relatively little is known about the in vivo behaviour of oligonucleotides. Extrapolations from in vitro studies to predict in vivo pharmacokinetics and effects in humans might be difficult and inappropriate. Animal models still remain an essential tool in the development of oligonucleotides as efficient drugs in humans.