ABSTRACT
Antisense therapeutic agents are moving from the research laboratory to the clinic. Antisense drugs are being used in a broad range of disease indications from viral infections, to cancer, to inflammatory diseases. The molecular targets range from viral transcription factors, and oncogenes, to cellular adhesion molecules. Many drugs are well beyond Phase I clinical trials, with the data on the safety and efficacy of the agents being analyzed. The cellular distribution of phosphorothioate oligonucleotides has been studied using autoradiography, immunohistochemistry, and fluorescent-tagged oligonucleotide. Phosphorothioate oligonucleotides can be envisioned to produce toxicity by several different mechanisms. The most obvious mechanism is a toxicity that is related to the knockdown expression of the target protein: exaggerated pharmacologic activity. Judicious selection of antisense targets is the best way to avoid toxicities related to the intended activity of the drug.
