6,6′-Trehalose dioleate (6,6′-TDO) is a glycolipid that has been used in the generation of lipid nanoparticles (LNPs) for the delivery of mRNA in vitro and in vivo.1 LNPs containing 6,6′-TDO and encapsulating mRNA encoding influenza A hemagglutinin A (HA) increase Ifn-γ, Il-2, and Tnf-α secretion by isolated mouse splenocytes. LNPs containing 6,6′-TDO accumulate in the liver and spleen after intramuscular administration in mice. Unlike LNP formulations that do not contain 6,6′-TDO, LNPs containing 6,6′-TDO do not decrease serum levels of blood urea nitrogen (BUN) or increase serum levels of lactate dehydrogenase (LDH), troponin I, alanine transaminase (ALT), and aspartate aminotransferase (AST) in mice. LNPs containing 6,6′-TDO and encapsulating mRNA encoding influenza A HA increase serum IgG1 and IgG2a titers in mice.
References:
[1]. Bae, S.-H., Yoo, S., Lee, J., et al.A lipid nanoparticle platform incorporating trehalose glycolipid for exceptional mRNA vaccine safetyBioact. Mater.38486-498(2024).