In this AVT issue, we would like to talk about the application of DMG-PEG2000 in RNA drug liposomes, a cationic lipid material,and what are the advantages of the new PEGylated lipid represented by DMG-PEG2000? Recently, AVT launched our new product DMG-PEG2000, this new lipid material which is known to everyone with the hot development of the new coronary pneumonia mRNA vaccine is rapidly becoming popular, many friends only know that it has the same long cycle effect and better gene transfection effect as DSPE-mPEG2000, but do not understand the specific principle behind it.
The full name of DMG-PEG2000 is 1,2-dimyristoyl-rac-glycero-3-methoxypolyethylene glycol-2000, which can be translated as dimyristoyl-glycero-polyethylene glycol 2000 in Chinese.Molecular formula is C122H242O50,Molecular weights 2509.2 (average value), with the following representative structure.
It can be seen from the structural formula that the material is modified by PEGylation with a short-chain lipid. C14 is much shorter than the C18 chain of common DSPE-mPEG2000. The most direct result of this is the insertion of lipid "anchor". The lipid film is relatively "shallow" and is easier to fall off during systemic circulation. The biggest advantage of this design is that it solves the "PEG-dilemma". PEG-dilemma has three main points:
1. The steric hindrance of the PEG chain shields the interaction between liposomes and cell membranes and inhibits the uptake of liposomes by target cells;
2. shields the interaction between liposomes and endosomal membranes It prevents the "escape of endosomes" and causes RNA to be degraded and cannot enter the cytoplasm smoothly;
3. Multiple injections of PEGylated liposomes induce immune responses and cause accelerated blood clearance (ABC).
The general solutions are: reduce the density of PEG on the liposome surface; use cleavable PEG-lipid linkers, such as ester bonds, hydrazone bonds, and peptide bonds; use short-chain lipids, such as C14 lipid anchoring. C18 is easier for PEG to dissociate from the particle surface. In addition, the short chain (myristic acid, C14) of DMG-PEG2000 has a shorter half-life than the long chain (stearic acid, C18) and can be degraded faster. DMG-PEG2000 can reduce the interaction between liposomes and cells and the adsorption of ApoE Ability to obtain the best cell gene silencing effect.
"Lysosome/endosomal escape" is the key and difficult point in the delivery of RNA drugs, and the efficacy of the drug is directly related to it. The use of polyethylene glycol lipids containing short alkyl chains can rapidly dissociate while achieving escape in the body, thereby preventing the failure of "endosome escape" caused by PEGylation. This is why DSPE-mPEG2000 is commonly used in chemical drug liposomes and nucleic acid liposomal drugs using DMG-PEG2000 have higher gene silencing/expression level and the best drug effect.
Based on this consideration, many new PEGylated lipids have been developed, such as DMA-PEG2000, PEG2000-Ceramide-C14, etc. You can choose them according to your needs in scientific research.
Attached a comparison of several PEGylated lipid structures
mPEG2000-DMG
mPEG2000-C16 Ceramide
mPEG2000-DSPE
Seeing this, you should know the application of DMG-PEG2000 in RNA drug liposomes! If you want to discuss and exchange with us, please call us: 400-6262 623!
(All Rights Reserved)