DLin-MC3-DMA, a key excipient for nucleic acid delivery, can ionize cationic lipids

Nucleic acid delivery of key exciciants DLIN-MC3-DMA can be ionized cationic lipid and has the characteristics of low toxicity and high efficiency is favored by the majority of pharmaceutical research friends, this issue of AVT xiaobian to give you a brief analysis of this favored cationic lipid DLIN-MC3-DMA!

Cationic liposome, as the name implies, is a positive particle of the liposome preparation, so providing positive charge of the cationic lipid is the key preparation. At present, the most common and widely used cationic lipids on the market are DOTAP, DOTMA, DC-Chol, etc., but they all have great cytotoxicity in application, so it is often difficult to balance the drug loading and safety.

Dlin-mc3-dma has a unique ph-dependent charge variable property: it is positive under acidic conditions and neutral under physiological pH conditions. Therefore, the nucleic acid is coated under acidic conditions and the resulting liposomes have a very small positive charge density in the blood, which means very low cytotoxicity. In addition, dLIN-MC3-DMA cationic liposomes can increase the lysosome escape of particles in vivo due to its positive charge, and improve the transfection efficiency, but it is not easy to be phagocytosed by macrophages. Using these characteristics, cationic liposomes prepared by DLIN-MC3-DMA have excellent performance in siRNA delivery with "low toxicity and high efficiency".

In addition, we found that the functional activity of cationic liposomes was particularly correlated with the pKa values of the cationic lipids used, and that cationic lipids with pKa values between 6.2 and 6.5 resulted in a very efficient gene silencing effect. Among many synthetic candidates, the effect of DLIN-KC2-DMA is better than that of DLIN-DMA, while the performance of DLIN-MC3-DMA is more outstanding. Compared with DLIN-DMA, the gene silencing activity in liver tissue cells is increased by three orders of magnitude. The ED50 of DLIN-MC3-DMA-LNP was further reduced without an increase in toxicity, so its successful application in Onpattro has become the key of Alnylam for siRNA delivery technology, and is the "standard" lipid material for the preparation of liver targeted siRNA/LNP system.

Onpattro is one of di's marketed siRNA liposome drugs for the treatment of familial transthyroxine protein amyloidosis (hATTR) in polyneuropathy, successfully opening the door to cell-silencing gene 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.

For more information on key excipatory materials for nucleic acid delivery, please pay attention to our official website avt-avt.com or call our 400 official telephone number: 400-6262-623. We look forward to your consultation!