Federal Grant Award Summary

The University of Pennsylvania received a $726,531 Project Grant awarded on June 15, 2026, by the National Heart, Lung, and Blood Institute (NHLBI) under the Cardiovascular Diseases Research program (CFDA 93.837). The grant supports research to identify mechanisms of lipid nanoparticle (LNP)-associated inflammation (LAI) and develop engineering solutions to create non-inflammatory LNPs. This research addresses a critical barrier to the clinical advancement of LNP-based therapeutics, which have demonstrated revolutionary potential in genetic medicine but face significant inflammatory complications that have halted clinical trials, including at companies such as Verve Therapeutics.

The primary deliverables include: (1) mapping the complex network of pathways that generate LNP-associated inflammation through literature review and experimental validation, and (2) developing and loading LNPs with newly synthesized fast-acting inhibitors of LAI to reduce inflammatory responses. The research builds upon the grant recipients' preliminary findings that local phagocytes are responsible for the majority of LNP-induced inflammation and that galectins—intracellular sensor proteins—recognize endosomal membrane damage and activate inflammatory pathways. The project runs through February 28, 2030, and is conducted at the University of Pennsylvania's facility in Philadelphia, Pennsylvania.