Pharmacology of antisense oligonucleotide inhibitors of protein expression

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 classes of drugs. For these opportunities to be fully capitalized upon, investigators must choose molecular targets for drug development that are likely to yield attractive therapeutic profil es. This will require rapid and effective determination of gene functions i n 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 wi ll likely prove useful as drugs. Tn this review, we discuss some of the iss ues surrounding the use of antisense oligonucleotides as research tools to help elucidate gene function, and highlight some of the approaches that can be taken to generate and use effective antisense reagents. (C) 1999 Elsevi er Science Inc. All rights reserved.