Progress in antisense therapeutics.

Antisense technology offers the potential to create compounds specific enough to support highly isotypically selective pharmacology (i.e., pharmacologic agents specific enough to affect only one isotype in a multigene family of related proteins). However, enthusiasm about the potential of the technology has been appropriately tempered by questions about its ability to deliver on its promise. The fundamental issue is: Can oligonucleotides that have acceptable drug properties be created? This review discusses recent progress that helps to define the pharmacokinetic, pharmacologic, and toxicologic properties of phosphorothioate oligonucleotides. Progress in the medicinal chemistry of oligonucleotides that has resulted in a wide range of new chemical classes is also described.