Improved localized mRNA delivery using lipid nanoparticles with a novel synthetic cholesterol derivative.

ABSTRACT: Lipid nanoparticles (LNPs) are self-assembled nanocarriers made up of ionizable cationic lipids, membrane lipids, sterols, and PEGylated lipids in a predetermined proportion to encapsulate nucleic acid payloads. According to recent findings, following local administration (intramuscular, intratumoral), LNPs diffuse into the systemic circulation and subsequently show liver transfection. Liver transfection can result in both liver toxicity and undesirable cargo distribution. To address this issue, we synthesized a novel cholesterol derivative, glutamate-cholesterol (GA-Chol), which, when incorporated in LNPs (GA-Chol LNPs), improved in vitro transfection efficiency by approximately 10-fold and 20-fold in HEK293T and HeLa cells, respectively. Furthermore, when GA-Chol LNPs were injecte

SUBMITTER: Sahel DK 

PROVIDER: S-EPMC12606572 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature