Reengineering Endogenous Targeting Lipid Nanoparticles (ENDO) for Systemic Delivery of mRNA to Pancreas.

ABSTRACT: Lipid nanoparticles (LNPs) hold transformative potential for nucleic acid delivery, with applications ranging from clinical use, particularly in COVID-19 vaccines, to gene therapy and cancer immunotherapy. However, a major limitation lies in their preferential accumulation in the liver following intravenous administration, making most targets hard-to-reach. In this study, a novel platform called endogenous targeting lipid nanoparticles (ENDO), containing cholecalciferol (vitamin D3) as a fifth component is reported, that selectively delivers mRNA to the pancreas - a target previously inaccessible through intravenous administration. The top formulation, C-CholF3, demonstrates an unprecedented 99% pancreas selectivity with robust and sustained protein expression for up to 3 days in a dose-de

SUBMITTER: Isaac I 

PROVIDER: S-EPMC12510295 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature