Federal Project Grant Award Summary

The National Institute of General Medical Sciences (NIGMS) awarded a $423,500 Project Grant to the Regents of the University of Minnesota, Office of Sponsored Projects Administration, effective July 1, 2026, through February 28, 2031, under the Biomedical Research and Research Training program (CFDA 93.859). The award funds the development of advanced mass spectrometry platforms designed to characterize the structural stability of three major therapeutic classes: monoclonal antibodies, messenger RNA (mRNA) therapeutics, and adeno-associated viruses (AAVs). This research directly addresses a critical gap in current biotherapeutic manufacturing and quality assurance by enabling molecular-level understanding of how these therapeutics degrade or lose efficacy under stress conditions.

The project deliverables include integrated mass spectrometry methodologies—specifically native mass spectrometry, ion mobility-mass spectrometry, charge detection mass spectrometry, and controlled activation techniques—coupled with complementary analytical approaches such as differential scanning fluorimetry and circular dichroism spectroscopy. For antibodies, the research will map how sequence variations, glycosylation patterns, and aggregation affect stability and antigen binding. For mRNA therapeutics, the work will establish the first mass spectrometry-based assays to quantify unfolding transitions of large transcripts and assess how lipid nanoparticle encapsulation influences stability. For AAVs, the research will define capsid destabilization pathways and genome release mechanisms through experimental validation and computational modeling. These analytical advances are intended to facilitate the design of more resilient biotherapeutics and improve manufacturing and storage protocols across the biomedical industry.