Chapter 15: Small-molecule Targeted Degradation of RNA

Small-molecule targeting of structural elements within disease-causing RNAs has garnered the interest of academia and the pharmaceutical industry. This chapter describes advances in the targeted degradation of RNA by structure-specific synthetic ligands that exploit natural products to cleave nucleic acids or compounds that locally recruit and activate endogenous ribonucleases to enzymatically cleave an RNA target. We describe the assembly process of RNA degraders and their application to validate mode of action and profile on- and off-targets. Finally, we outline future challenges for RNA degraders, including their application to the precise degradation of disease-causing RNAs, and highlight their therapeutic potential.