Genevant CL1 (lipid 10) is a novel ionizable lipid for rna delivery.Lipid 10 rapidly accumulated in the liver within the first hour of dosing (reflecting LNP uptake), but levels then steadily declined over the ensuing 2 weeks period, similar to MC3.Lipid 10 afforded more than double the expression of either approved lipid. We also observed high splenic expression for ALC-0315, which correlated with higher MCP-1 levels.Animals received a single 5 µg IM dose of LNP encapsulating firefly luciferase (fLuc) mRNA. Whole body imaging was performed 6 h later and expression at the injection site quantified. Lipid 10, ALC-0315, and SM-102 showed similar expression at the injection site, all greater than the older generation benchmarks lipids (DLinDMA, KC2, MC3). Lipid 10 and ALC-0315 also showed high expression in the liver, while SM-102 was less, and more similar to MC3.Lipid 10-based LNP reported similar anti-HA IgG titers to MC3 and ALC-0315 (Comirnaty) LNP, and higher than the SM-102 (SpikeVax) LNP composition. MCP-1 levels were generally similar, although the ALC-0315 composition had a significantly higher response at the 5 µg dose. All formulations reported good stability when stored frozen at −80 °C or at 2–8 °C for 1 month.
Cat.No
DC59126
Name
Genevant CL1 (lipid 10)
Chemical Properties
CAS
1450888-71-7
Formula
C39H73NO2
MW
588.00
Storage
-20
References
Unsaturated, Trialkyl Ionizable Lipids are Versatile Lipid-Nanoparticle Components for Therapeutic and Vaccine Applications
Kieu Lam, Ada Leung, Alan Martin, Mark Wood, Petra Schreiner, Lorne Palmer, Owen Daly, Wenchen Zhao, Kevin McClintock, James Heye-- 21 January 2023 https://doi.org/10.1002/adma.202209624
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