As a new cationic lipid -- ionizable cationic lipid, DLIN-MC3-DMA has the advantage of "low toxicity and high efficiency", and has attracted much attention with the launch of Onpattro, a siRNA liposome product from Shou in the United States. It is chemically known as 4-(N, N-dimethylamino) butyric acid (6Z,9Z,28Z,31Z) -hepty30 carbon -6,9,28, 31-tetra-19-base, molecular formula C43H79NO2, is a colorless to light yellow oily liquid, pKa=6.44.
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Cationic liposomes, as the name implies, are liposome preparations with positive electric properties, so providing positive electric properties of cationic lipids is the key to preparations. At present, the most common and commonly used cationic lipids in the market are DOTAP, DOTMA, DC-CHOL, etc., but they all have greater cytotoxicity in the application, so it is often difficult to balance the two aspects of drug loading and safety.
DLIN -MC3-DMA has a unique pH-dependent charge variable property: it is electrically positive under acidic conditions and electrically neutral under physiological pH conditions. As a result, nucleic acids are encapsulated in acidic conditions and the resulting liposomes have a very low positive charge density in the blood, i.e. low cytotoxicity. Moreover, DLIN-MC3-DMA cationic liposome can increase the lysosomal escape of particles in vivo and improve the transfection efficiency, but it is not easy to be phagocyted by macrophages because of its positive electricity. Using these characteristics, the cationic liposomes prepared by DLIN -MC3-DMA have excellent performance of "low toxicity and high efficiency" in siRNA delivery.
In addition, we found that the functional activity of cationic liposomes was particularly correlated with the PKA value of the cationic lipids used, with a PKA between 6.2 and 6.5 producing a highly efficient gene silencing effect. In many synthesis of candidates, DLin KC2 - DMA is better than DLin - DMA, and DLin - MC3 - DMA performance is more outstanding, compared with DLin - DMA liver tissue cell gene silencing activity for improvement of the three orders of magnitude, DLin - MC3 - DMA - LNP ED50 further reduce, not increase, therefore with its successful application in Onpattro, be it for key siRNA delivery technology, preparation of liver targeting siRNA/LNP system is "standard" of lipid material.
Onpattro for the zhi treatment of familial transthyroxine amyloidosis (Hattr) multiple neuropathy, DI is a marketed siRNA liposome drug, successfully opening the door to cell gene silencing drugs. Almost any disease can express good through pathological gene, protein or edit the way such as defective genes to zhi, therapy, the application of cationic liposomes nanoparticle delivery systems is not only confined to the liver cells, can also be silence genes in other organizations, and even cause ai genes, can develop as a platform technology, very has the prospect of application.
Cationic liposome DLIN -MC3-DMA spot sales, welcome to inquire: 400-6262-623
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