Developing antisense oligonucleotides from the laboratory to clinical trials

Antisense gene therapy has attracted the attention of the pharmaceutical industry with its promise of simple and specific rational drug design. These 'informational drugs' uniquely target gene expression, unlike traditional therapeutics, which block activity of an existing protein. Oligonucleotide therapies are now developing a strong proof-of-concept foundation based on in vitro and animal models, and several clinical trials in progress aim to demonstrate that these compounds can be safe and effective drugs. With pharmacodynamic, toxicological and efficacy data accumulating from animal and human studies, the critical goals are to enhance compound delivery and stability, and reduce the nonspecific toxic effects of these rational therapeutics.