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  • The therapeutic use of messenger RNA (mRNA) holds great promise to combat a wide range of incurable diseases. Especially for rare genetic metabolic diseases, mRNA therapy is considered an alternative to protein replacement therapy. In addition, the mRNA has showed therapeutic potential in many other applications, including virus vaccine, cancer immunotherapy, cellular reprogramming and genome editing. To achieve a therapeutic effect, mRNA molecules must reach specific target cells and produce sufficient amounts of the protein of interest. Therefore, safe and effective mRNA delivery materials are essential for targeted delivery and endosomal escape of mRNA delivery systems.

    Various materials for mRNA delivery have been developed, including lipids and similar materials, polymers, and protein derivatives. Lipid nanoparticles (LNPs) have been intensively studied and emerged as a promising vehicle for the delivery of mRNA. The LNPs are mainly composed of cationic ionizable lipids (CILs) together with the helper lipids, cholesterol, phospholipids, and polyethylene glycol (PEG)-functionalized lipids (PEG-lipids). LNPs have a core–shell structure. The outer shell is composed of a hydrated PEGylated layer and the inner shell contains cholesterol, phospholipids, and CILs. The lipids can improve LNP properties such as particle stability, delivery efficiency, tolerance, and biodistribution. In LNPs, CILs are keys to formulating nanoparticles that have colloidal stability and can be efficiently delivered into the cell with low toxicity. SM-102, DLin-MC3-DMA and ALC-0315 are popular CILs used to encapsulate RNA. DOPE and DSPC are two commonly used helper phospholipids for LNP formulation. Studies have found that LNPs containing DOPE preferentially accumulate in the liver, whereas identical LNPs containing DSPC instead of DOPE preferentially accumulate in the spleen.


    Amerigo Scientific offers a variety of lipid materials to form LNPs for mRNA delivery.

    Polyethylene glycols (PEGs) are hydrophilic non-ionic polymers formed by the polymerization of ethylene oxide under alkaline catalysis. PEGs exist in a linear or branched chain structure. PEG-lipids, also known as PEGylated lipids have multiple effects on the properties of LNPs. The amount of PEG-lipid can affect particle size and zeta potential. PEG-lipids can further promote particle stability by reducing particle aggregation, because of the high solubility provided by PEG chains in aqueous media. This solubility creates a "conformational cloud" that prevents interactions with other PEGylated LNPs, reduces aggregation, and provides a high degree of stability. Certain PEG modifications can reduce the clearance mediated by the kidney and monocyte-macrophage system (MPS) to prolong the blood circulation time of LNPs. In addition, PEG-lipids can be used to conjugate specific ligands to particles for targeted delivery. The extent of these effects depends on the proportions and properties of PEG-lipids, such as PEG molar mass, lipid length, and the conformation. For example, high molecular weight PEGs have stronger hydrophilicity and flexibility as well as larger steric hindrance than short PEGs, resulting in a thicker protective layer that avoids interactions with biomolecules.

    PEGylated Derivatives

    Amerigo Scientific offers a variety of PEGylated derivatives including PEG-lipids to prepare LNPs for mRNA delivery.

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