RNA as a Drug Target

Abstract

Historically, the pharmaceutical industry has focused on proteins, rather than nucleic acids, as drug targets. But recent advances in the fields of RNA synthesis, structure determination and therapeutic target identification make the systematic exploitation of RNA as a drug target a realistic goal. RNA folds into complex structures that can interact specifically with effector proteins. These interactions are essential for various biological functions. It is now fully recognized that RNA molecules intervene at all stages of cell life, not only because of key sequence motifs but also because of intricate three dimensional folds. This realization has promoted RNA to a potential therapeutic target. Bacterial ribosomal RNA is the target of clinically important antibiotics, while biologically important RNAs in viral and eukaryotic genomes present a range of potential drug targets. While targeting of RNA for drug design is very challenging, continuing advances in our understanding of the principles of RNA–ligand interaction will be necessary to realize the full potential of this class of targets. The application of new biochemical screening and design based technologies, coupled with a resurgence of interest in phenotypic screening, has resulted in several compelling successes in targeting RNA.