Drug discovery using the regulation of gene expression

The expression of a disease-relevant protein is controlled by a transcriptional program specifically regulated at all stages of normal development and during the adult life. Thus, regulation of gene expression as an approach to drug discovery is conceptually appealing because it provides a rational basis for molecular strategies aimed at modulating gene expression in given cell types and/or at a given time. Indeed, numerous pharmacologic agents have been identified that can either restore or suppress disease-relevant protein expression. In this review, the author critically examines new strategies and methodologies that are being used and developed to identify and validate new therapeutic targets by taking advantage of our knowledge on mechanisms regulating their expression at the transcriptional and post-transcriptional levels. The author also examines the impact of genome-wide approaches and methods aimed at controlling epigenetic mechanisms of gene regulation and concludes by extrapolating on future trends.