A Chemoinformatic-Guided Synthesis of a Spleen-Expressing mRNA Lipid Nanoparticle Platform.

ABSTRACT: mRNA lipid nanoparticles (LNPs) are a powerful technology that are actively being investigated for their ability to prevent, treat, and study disease. However, a major limitation remains: achieving extrahepatic mRNA expression. The development of new carriers could enable the expression of mRNA in non-liver targets, thus expanding the utility of mRNA-based medicines. In this study, we use a combination of chemoinformatic-guided material synthesis and design of experiment optimization for the development of a spleen-expressing lipid nanoparticle (SE-LNP). We begin with the synthesis of a novel cholesterol derivative followed by SE-LNP formulation and design of experiment-guided optimization to identify three lead SE-LNPs. We then evaluate their in vitro delivery mechanism, in vivo

SUBMITTER: Narasipura EA 

PROVIDER: S-EPMC12312780 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature