Federal Grant Award Summary

The University of Connecticut received a $607,470 Project Grant from the National Institute of General Medical Sciences (NIGMS) under the Biomedical Research and Research Training program (CFDA 93.859), effective March 1, 2026 through February 28, 2030. The project, titled "Enabling Mass Spectrometry-Based Mid-Down Sequencing of Large Modified RNAs," aims to develop advanced analytical methodologies to address critical limitations in characterizing covalently-modified nucleic acids used in emerging biotherapeutics and non-coding regulatory RNAs. The research team will advance mass spectrometry (MS) technology by utilizing RNA-cleaving deoxyribozymes with superior sequence specificity to control the fragmentation of large RNA molecules, enabling the analysis of analytes exceeding several thousand nucleotides—a capability currently constrained by conventional genomics techniques.

The project will deliver a toolkit of deoxyribozymes with variable target motifs and will re-examine capillary electrophoresis (CE) coupled with MS detection to optimize oligonucleotide separation and analysis. By controlling mixture complexity through targeted cleavage strategies and exploring alternative separation chemistries, the research will provide a practical analytical platform that fills a critical gap in the characterization of large, modified nucleic acid biotherapeutics and regulatory RNAs. These deliverables will expand the practical size range of oligonucleotides amenable to direct gas-phase sequencing and enable mid-down characterization of complex RNA molecules.