C14-4, an ionizable cationic lipid with a pKa of 6.5, has been employed in lipid nanoparticles (LNPs) for mRNA delivery. These LNPs, containing C14-4 and mRNA encoding a chimeric antigen receptor (CAR), effectively induce CAR expression in human T cells ex vivo, comparable to electroporation but with less toxicity. Additionally, they exhibit cytotoxicity against Nalm-6 leukemia cells in vitro. The pKa is 6.51.
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