Pharmacological Activity of Antisense Oligonucleotides in Animal Models of Disease

Abstract

Over the last 20 years, antisense oligonucleotide approaches have proven to be extremely valuable methods for characterizing the function of specific gene products and for addressing and optimizing antisense mechanisms of action. Numerous reviews have been published describing some of the accomplishments in this area, some of which are cited here (;;;). However, it has only been within the last 5–7 years that antisense technology has progressed such that the therapeutic value of these compounds can be evaluated in animal models of human disease. Over this period, reports demonstrating pharmacological activities of antisense oligonucleotides in animal models have accelerated at an impressive rate in a number of therapeutic areas, most commonly cancer, restenosis, and inflammation. In many of these studies, the pharmacological activity reported for the antisense oligonucleotides was very controlled such that it is difficult to ascribe a mechanism of action other than antisense. Many of these studies have been included in prior reviews of the antisense field (;;).