Lipids

Harashima group from Hokkaido University developed a hepatocyte-specific drug delivery system called multifunctional envelope-type nanodevice (MEND) which gives improved siRNA endosomal escape efficiency. The three generations of the pH-responsive ionizable lipid of the MEND system are YSK05 (2012 pKa 6.4) YSK13 (2016 pKa 6.45) and CL4H6 (2019 pKa 6.25). The ED50 of Factor VII knockdown after the intravenous injection of YSK05 YSK13 and CL4H6 LNPs into mice were shown to be 60 ug/kg 15 ug/kg 2.5 ug/kg respectively.

ssPalmE-P4C2 is an ionizable lipid with a Vitamin E scaffold that is used to formulate lipid nanoparticles (LNPs) for delivering RNA into cells. The Vitamin E scaffold acts as an adjuvant to activate innate immune signaling. Vaccination with ssPalmE-P4C2 containing LNPs protected against lethal infection by Toxoplasma gondii in a mouse model.

244cis is an ionizable lipid for forming lipid nanoparticles (LNPs) which allow the repeated dose of mRNA without the loss of activity due to its low immunogenicity. 244cis LNPs has potential for the treatment of chronic diseases in the lung with improved potency and safety.

6 6’-trehalose dioleate is a glycolipid which can reduce toxicity when incorporated into lipid nanoparticles (LNPs). It can form hydrogen bonds with polar biomolecules allowing the formation of a stable LNP structure by partially replacing the ionizable lipid. It can facilitate the development of safe mRNA vaccines with improved clinical safety.

6-Trehalose monooleate can be used as antiaggregation agent for stabilization of proteins. It can also be used as a delivery vehicle for topical drugs by forming solid lipid nanoparticles.

C12-113 is an ionizable lipid used to formulate lipid nanoparticles (LNPs) for delivering RNA to cells. C12-113 LNPs delivered mRNA encoding luceriferase and the SARS-Cov2 spike protein into a mouse model.

Lipid M is an ionizable lipid used to form lipid nanoparticles for delivering RNA. LNPs formulated with Lipid M delivered luciferase mRNA in mice resulting in higher protein expression compared to the benchmark lipid DLin-MC3-DMA. Lipid M LNPs delivering IgG mRNA showed prolonged expression compared to MC3 in non-human primates after intramuscular injection.

4-O10b1 is an ionizable lipid used to generate lipid nanoparticles (LNPs) for delivering RNA to cells. LNPs comprised of 4-O10b1 and conjugated with the macrophage antibody F4/80 were able to delivery siRNA targeting TAK1 to RAW264.7 cells resulting in suppressed activation of NF-kB. Intranasal administration reduced lung injury in an influenza mouse model.

FTT5 (Echelon Cat#: N-1115) is an analog of TT3 (Echelon Cat#: N-1113). FTT5 lipid nanomaterials (LNPs) displayed two-fold potency in the delivery efficiency of mRNA to the liver compared to TT3 LNPs. FTT5 LNPs efficiently delivered long mRNAs such as human factor VIII (hFVIII) mRNA (~4.5 kb) for expression of hFVIII protein in hemophilia A mice in vivo.