YHS-12 is an ionizable cationic lipid (pKa = 6.506) that has been used in the generation of lipid nanoparticles (LNPs) for the delivery of siRNA and mRNA in vitro and in vivo.1 LNPs containing YHS-12 and the macrophage targeting peptide CRVLRSGSC and encapsulating mRNA encoding chimeric antigen receptor targeting methicillin-resistant S. aureus (MRSA) and siRNA targeting caspase-11 increase the phagocytosis rate of MRSA in RAW 264.7 macrophages and primary mouse bone marrow-derived macrophages (BMDMs). Intravenous administration of these LNPs decreases blood bacterial burden and increases survival in a model of sepsis using cyclophosphamide-induced immunosuppressed mice.
References:
[1]. Tang, C., Jing, W., Han, K., et al.mRNA-laden lipid-nanoparticle-enabled in situ CAR-macrophage engineering for the eradication of multidrug-resistant bacteria in a sepsis mouse modelACS Nano18(3)2261-2278(2024).