Pharmacology of antisense oligonucleotides

The dramatic increase in recent years of both the amount and rate of accumulation of novel genomic sequence information has generated enormous opportunities for the development of new drug classes. For these opportunities to be fully capitalized upon, investigators must choose molecular targets for drug development that are likely to yield attractive therapeutic profiles. This process will require rapid and effective determination of gene functions in multiple cellular settings. The development of antisense oligonucleotides as specific inhibitors of gene expression should allow such determination of gene function. In addition, the antisense oligonucleotides themselves are being developed as drugs. In this review we discuss some of the issues surrounding the pharmacology of antisense oligonucleotides both as research tools and as drugs, and highlight some of the approaches that can be taken to generate and use effective antisense reagents.