Session: Tech Forum Innovative Cationic Lipids for RNA Delivery Unlocking New Extra-Hepatic Horizons with Tailored 4-Lipid and 5-lipid LNP Formulations
Tech Forum: Innovative Cationic Lipids for RNA Delivery Unlocking New Extra-Hepatic Horizons with Tailored 4-Lipid and 5-lipid LNP Formulations
Tuesday, July 9, 2024
8:00 AM - 9:00 AM CET
Location: Orange
Sponsored By
Lipid nanoparticles (LNP) have demonstrated high efficiency delivering RNA therapeutics in vivo. However, the properties of such nanoparticles obtained with conventional ionizable lipids are often hard to modulate; particularly their biodistribution profile. As a result, ionizable LNPs often predominantly end up targeting and accumulating in the liver.
One of the current challenges in the field consists of adjusting the chemical composition of the LNPs to the intended application. Here, we characterized a library of innovative imidazolium-based cationic lipids as key component of cationic LNPs (cLNP). We disclose their chemical structures and demonstrate their efficacy in generating LNPs through characterization of their hydrodynamic diameters, zeta potentials, and mRNA encapsulation efficiencies. The resulting nanoparticles display high in vitro transfection efficiencies and have little to no impact on cell viability, on HEK293 and CaCo-2 cell lines.
In addition, these cationic lipids can either fully substitute the ionizable lipid or be added as a supplementary 5th lipid in LNP formulations, conferring an overall positive charge to LNPs and enabling in vivo extra-hepatic biodistribution. Also, their diverse chemical structures offer a unique opportunity to fine-tune the efficacy and biodistribution of LNPs to meet specific therapeutic needs.
