Comparative Pharmacokinetics of Antisense Oligonucleotides

Antisense oligonucleotides have attracted special interest as a novel class of therapeutic agents for the treatment of viral infection, cancers, and genetic disorders because of their ablhty to inhibit expression of a disease-associated gene in a sequence-specific manner. Gene expression is inhibited by hybrid ization of the oligonucleotide to sequences in the gene or the messenger RNA (mRNA) target by Watson-Crick base pairing. The first example of specific mhibition of gene expression by an ohgonucleotide was reported by Zamecnik and Stephenson (1 ), who demonstrated that a short oligonucleotide inhibited Rous sarcoma virus replication in cell culture. Since then, the field has progressed enormously. Numerous studies have demonstrated the ability of antisense oligonucleotides to modulate gene expression (2 –4 ). Accompanying chapters in this volume describe the use of antisense oligonucleotides for vanous disease targets.