Project Grant R21AI199121

Grant Award Summary

The University of Chicago received a $442,296 Project Grant award from the National Institute of Allergy and Infectious Diseases (NIAID) under the Allergy and Infectious Diseases Research program (CFDA 93.855), with an award date of June 9, 2026 and completion date of May 31, 2028. The grant supports the development of RNA-degrading chimeras (RDCs)—a novel class of antiviral molecules designed to selectively bind viral RNA and cleave it directly through acid-base catalysis, mimicking the function of natural ribonucleases. The research addresses limitations of existing RDC approaches that achieve only partial RNA knockdown by creating direct-acting antivirals capable of more complete viral degradation.

The deliverables include optimization of RNA-binding selectivity targeting conserved viral structures, establishment of a high-throughput synthesis and screening pipeline, and implementation of second-generation chemical-guided shape sequencing (CGSHAPE-SEQ) technology for activity-based RNA profiling across the transcriptome. The research will demonstrate effectiveness of the optimized RDCs using Zika virus (ZIKV) as the model system, with validation in both in vitro assays and ZIKV-infected human neural progenitor cells. This research represents the first application of RDCs to directly degrade ZIKV RNA and establishes a generalizable, scalable platform for RNA-targeting antiviral drug discovery applicable to emerging RNA viral threats.