SBIR Phase I: Multiplexed High Throughput Discovery of Functional RNA-Targeting Small Molecules Via Next-Generation Sequencing

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to address currently untreatable diseases by developing small molecule drugs that modulate RNA. Despite advances in genomic medicine, many disease-causing proteins remain undruggable using conventional approaches. By targeting RNA instead of proteins, this project could enable therapeutic interventions for diseases lacking treatment options, including certain cancers and neurological disorders. The technology platform will provide a scalable method to identify RNA-targeting small molecules, accelerating drug discovery and potentially creating a new class of oral medications. The commercial impact extends beyond therapeutic applications, as the screening platform could become an industry-standard tool for RNA drug discovery, stimulating broader pharmaceutical innovation. This Small Business Innovation Research (SBIR) Phase I project aims to develop a next-generation sequencing platform for discovering small molecules that target RNA. The project addresses two challenges: demonstrating that small molecules binding to messenger RNA can modulate protein expression in cells, and developing a high-throughput screening method to identify such molecules and their optimal RNA targets. The research will establish an assay that can detect RNA-drug interactions and identify which RNA structures are most amenable to binding. The technical approach integrates RNA biochemistry with next-generation sequencing to create a multiplexed screening platform. If successful, this project will establish a novel approach to RNA-targeted drug discovery, providing starting points for developing therapies against disease targets previously considered undruggable. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.