Chemical Probes to Control RNA Function

Abstract

Although traditional methods for drug discovery follow a protein-centric view, emerging studies on the importance of RNA have shed light on the need for a new category of therapeutics: RNA-targeted molecules. Their dysregulation has been associated with many different types of diseases, including cancer, neurological disorders and neurodegenerative diseases, illuminating the need to study chemical intervention that focuses on RNA. This new class of therapeutics would rely on targeting higher order RNA structures such as pseudoknots, triple helices and stem-loops to affect all levels of RNA regulations. Recent studies have demonstrated the feasibility of developing unique and specific RNA-targeting compounds translatable into therapeutics. This can happen through modulation of target genes or by targeting new classes of non-coding RNAs including a class of non-coding RNAs that are directly translated. Most methods currently developed to target RNA rely on high-throughput screening of chemical libraries. This chapter describes methods currently in use for targeting RNA and advocates greater use of in silico methods for developing such chemical entities.