Pharmacology of antisense oligonucleotides

The dramatic increase in recent years of both the amount and rate of accumu lation of novel genomic sequence information has generated enormous opportu nities 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 functio ns in multiple cellular settings. The development of antisense oligonucleot ides as specific inhibitors of gene expression should allow such determinat ion of gene function. In addition, the antisense oligonucleotides themselve s are being developed as drugs. In this review we discuss some of the issue s surrounding the pharmacology of antisense oligonucleotides both as resear ch tools and as drugs, and highlight some of the approaches that can be tak en to generate and use effective antisense reagents.