Lipids

Cardiolipin is an important component in prokaryotic  and in eukaryotic inner mitochondrial membrane.1  In humans CL is made by cardiolipin synthase from phosphatidylglycerol and cytidinediphosphate-diacylglycerol. 2  Due to its four acyl chains and small head group CL can organize into domains which can be proton sinks fill cavities at protein interfaces stabilize protein oligomers and participate in high-curvature membrane regions.  Autoantibodies to CL have been found in patients with anti-phospholipid syndrome and lupus3.

Lipid A6 is an ionizable and biodegradable lipid. Lipid A6 has similar structure as Dlin-MC3-DMA but with ester and alkyne bonds to improve its biodegradability and cell membrane fusion ability. Lipid A6 forms lipid-like nanoparticles together with cKK-E12 synergistically to facilitate robust mRNA delivery with improved tolerability. MC3 is the key delivery nanoparticle component of the first siRNA drug Onpattro.

Lipid 319 is an ionizable and biodegradable lipid. Lipid 319 nanoparticles have better delivery efficacy and biodegradability than DLin-MC3-DMA in the delivery of mRNA in vivo. MC3 is the key delivery nanoparticle component of the first siRNA drug Onpattro.

cKK-E12 is an ionizable lipomer that has been used in combination with other lipids in the formation of lipid nanoparticles (LNPs) for the delivery of mRNA. Reagent grade, for research use only.

4A3-SC8 is an ionizable lipid dendrimer used in generating lipid nanoparticles (LNPs) for RNA delivery. Incorporation of differently charged lipids (DODAP DOTAP or PA) into 4A3-SC8 LNPs allow for selective delivery of RNA to the liver lungs or spleen.

93-O17S is a lipidoid used for generating lipid nanoparticles to deliver RNA peptides and nucleotides. 93-O17S LNPs were able to deliver Cre recombinase mRNA in mice. In addition LNPs were able to deliver the Cre recombinase protein and Cas9:single-guide RNA into cells for genome editing. 93-O17S LNPs were used to deliver the STING pathway agonist 2′3′-Cyclic GMP-AMP (cGAMP) when injected into B16F10 tumors in mice which has potential as an in situ cancer vaccine.

AA3-DLin is an ionizable lipid used in generating lipid nanoparticles (LNPs) for RNA delivery. Unlike LNPs formulated with other ionizable lipids AA3-DLin LNPs performed best with higher proportions of phospholipid and lower cholesterol (40:40:25:0.5 AA3-DLin/DOPE/cholesterol/DMG-PEG). AA3-DLin containing LNPs were able to deliver full-length SARS-COV2 spike protein mRNA to BALB/c mice and generate a strong immune response.

Lipid C24 is an ionizable lipid that can be formulated into lipid nanoparticles for delivery of RNA. Lipid C24 LNPs containing mRNA encoding SARS-CoV-2 Spike protein generated 10X higher binding and pseudoneutralizing antibodies than DLin-MC3-DMA LNPs and showed less injection site inflammation.Reference: US 2022/0218622 A1 "Ionizable lipids and methods of manufacture and use thereof"

YSK05 is an ionizable lipid which is used to make lipid nanoparticles for delivery of siRNA. YSK05 LNPs delivered siRNA to hepatocytes and demonstrated gene silencing after intravenous administration.