Project Grant R01DK146271

Project Grant Award Summary

The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) awarded $742,478 to Icahn School of Medicine at Mount Sinai on July 15, 2026, under the Diabetes, Digestive, and Kidney Diseases Extramural Research program (CFDA 93.847) to conduct basic biomedical research on mRNA and lipid nanoparticle (RNA-LNP) therapeutics. The five-year project, extending through May 31, 2031, will elucidate the mechanisms by which RNA-LNP transfection and expression in professional antigen-presenting cells and non-professional cells—specifically hepatocytes and skeletal myocytes—modulate T cell immune responses to RNA-encoded proteins. The research aims to establish design principles for RNA-LNP therapeutics that can more precisely and safely control immune outcomes, ultimately improving the safety and efficacy of cancer and CAR T cell vaccines.

The project leverages preliminary findings demonstrating that hepatocyte and muscle fiber expression of RNA-LNPs actively participate in immune regulation, with hepatocyte expression suppressing antigen-specific T cells while muscle fiber expression enhances them. Deliverables will include mechanistic characterization of these cell-type-specific immune modulation pathways and the development of synthetic microRNA-targeting strategies to mitigate hepatic and muscle cell toxicity. This research contributes to the NIDDK's programmatic focus on fundamental and clinical studies addressing etiology, pathogenesis, and treatment of diabetes and metabolic disorders.