Organic Chemistry Seminar: Targeting RNA complexes with small molecules: to bind or to degrade?

Abstract:

Once considered mere intermediaries in protein synthesis, RNAs are now recognized as key regulators of cellular processes. The discovery of catalytic RNAs and diverse non-coding RNA species has revealed RNA as a highly dynamic and functional biomolecule. With nearly 70% of the human genome transcribed into RNA—and only a fraction encoding proteins—RNA represents a vast and largely unexplored frontier for therapeutic development, particularly given the limitations of current protein-targeting drugs. Our research centers on the design of small molecules that either bind to or induce the degradation of pathogenic RNA complexes. These targets include oncogenic microRNAs, long non-coding RNAs, RNA-binding protein complexes, mutated mRNAs, and other structured RNAs involved in cancer, aging, neurodegeneration, genetic disorders, and infectious diseases. We employ a wide range of technologies that enable us to recruit endogenous ribonucleases or exploit ubiquitination pathways, thereby promoting the selective degradation of toxic RNA complexes. In parallel, we explore binding strategies that modulate RNA function without degradation, offering complementary therapeutic routes. Guided by evolutionary principles and structure-function relationships, our goal is to discover high-affinity and selective RNA-targeted molecules

Event Organizer: Dr. Muhammad Jbara