Stabilizing Anionic mRNA Lipid Nanoparticles by Cleavable Crosslinking of Cholesterol
Yunhe Su; Joseph Choy; Xiang Liu; Yining Zhu; Jinghan Lin; Christine Wei; Kailei D. Goodier; Di Yu; Leonardo Cheng; Milan Patel; Xiaoya Lu; Jingyao Ma; Jialiang Wang; Hai-Quan Mao
ACS Applied Materials & Interfaces · DOI 10.1021/acsami.6c06888
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.
Why it is included: Expands accessible anionic formulation space for spleen delivery; crosslinker clearance, repeat dosing, and manufacturing comparability still need evaluation.