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An amidine-incorporated degradable lipid (pKa 8.15), has been used in the generation of LNPs for the delivery of siRNA and mRNA in vitro or in vivo, LNPs containing lipid 12T-O14 and encapsulating GFP-targeting siRNA reduce GFP levels in HepG2-GFP cells, intramuscular delivery of LNPs containing lipid 12T-O14 and encapsulating SARS-CoV-2 spike-encoding mRNA increases anti-SARS-CoV-2 spike protein IgG titers in mice in a prime and boost immunization regimen, LNPs containing lipid 12T-O14 accumulate in the liver, but LNPs containing both lipid 12T-O14 and MC3 can be tuned to target the lungs or the spleen. Formulation: A solid. InChI: InChI=1S/C37H66N2O2S/c1-3-5-7-9-11-13-14-15-16-18-20-22-31-41-37(40)30-33-42-32-23-25-36(38)39-35-28-26-34(27-29-35)24-21-19-17-12-10-8-6-4-2/h26-29H,3-25,30-33H2,1-2H3,(H2,38,39). InChIKey: JHGSICJQTCTZTQ-UHFFFAOYSA-N. SMILES: N=C(NC1=CC=C(C=C1)CCCCCCCCCC)CCCSCCC(OCCCCCCCCCCCCCC)=O
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