HNC2440 is an ionizable lipid designed for the assembly of lipid nanoparticles (LNPs) for nucleic acid delivery. It complexes with negatively charged RNA and co-assembles with phospholipids, cholesterol, and PEG lipids to form LNPs. Following cellular uptake via endocytosis, the RNA-loaded particles escape from endosomes and release their cargo, after which the liberated mRNA is translated into protein by ribosomes. HNC2440 is characterized by high delivery efficiency and rapid clearance.

Specifications

Application

For the in vitro and in vivo studies, LNPs were formulated at a molar ratio of HNC2440 : cholesterol : DSPC : DMG-PEG2k = 48.5 : 38.9 : 11.1 : 1.5 with an N/P ratio of 4.84, and encapsulated using a microfluidic mixing process.

Figures

1. Delivery Efficiency

The delivery efficiency of Fluc mRNA LNP (left) and Gluc mRNA LNP (right) prepared with HNC2440 in mice is comparable to that of LNPs prepared with a clinically used ionizable lipid.

Figure 1. Delivery efficiency of Fluc mRNA LNP and Gluc mRNA LNP prepared with HNC2440 in mice

2. Clearance in Liver and Spleen

Following tail-vein injection of 0.1 mg/kg Fluc mRNA LNP, residual ionizable lipid levels in the liver and spleen were measured at multiple time points. HNC2440 was cleared from both organs significantly faster than the clinically used ionizable lipid.

Figure 2. Residual ionizable lipid in the liver and spleen after intravenous administration of Fluc mRNA LNP