Antisense comes of age.

During the last ten years, antisense technology has experienced growing pains not unlike those of adolescence. In 1992, antisense was trumpeted as one of the top 10 emerging research areas. However, 3 years later, researchers were confronted with significant problems associated with antisense oligonucleotides ranging from sequence-dependent, non-antisense effects in vitro to dose-limiting toxicities in preclinical models [1-3]. Many researchers had doubts whether sequence-specific antisense even existed or whether it would ever exist as a therapeutic strategy [4]. Despite these gloomy predictions, many of the challenges facing the development of antisense-based drugs as therapeutics have been overcome as evidenced by the progress of several antisense oligonucleotides in the clinic for the treatment of cancer.