Stabilizing Anionic mRNA Lipid Nanoparticles by Cleavable Crosslinking of Cholesterol
Acid-cleavable cholesterol-derived crosslinkers and PEG-diamines stabilized anionic LNPs that otherwise lost activity during purification. By tuning crosslinking architecture, researchers balanced structural integrity with RNA release and improved splenic mRNA expression. Mechanistic analyses implicated intracellular processing as well as release behavior. These formulation-specific animal results do not establish general T-cell targeting or clinical manufacturing readiness.
DOI: 10.1021/acsami.6c06888