244cis is an ionizable cationic lipid (pKa = 6.3) utilized in the development of lipid nanoparticles (LNPs). In mice, LNPs containing 244cis and an mRNA reporter preferentially accumulate in the lungs and result in lower serum chemokine (C-C motif) ligand 2 (Ccl2) levels compared to LNPs with SM-102. Intravenous administration of 244cis-based LNPs encapsulating mRNA encoding Cre recombinase increases tdTomato fluorescence in lung endothelial, epithelial, and immune cells, as well as fibroblasts, in mice engineered with a floxed STOP codon to prevent tdTomato expression. Furthermore, LNPs with 244cis and siRNA targeting G2 and S-phase expressed 1 (Gtse1) reduce hepatic fibrosis, decrease Il-6 and Tnf-α production, and lower alanine transaminase (ALT) and aspartate aminotransferase (AST) levels compared to SM-102-based LNPs in a mouse model of carbon tetrachloride-induced liver injury.
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