mRNA vaccines are using a promising technology and an alternative option to conventional vaccine approaches. Some of their benefits include their low-cost manufacture, high potency, safety, and rapid development. The mechanism by which they work in the human body is by triggering the immune system leading to the development of antibodies and cytotoxic T cells. However, some of their drawbacks included their instability and inefficient in vivo delivery of mRNA. The key to an effective mRNA vaccine is efficient in vivo delivery which is provided by lipid nanoparticles. They can facilitate endosomal escape. They can be targeted to the selected cell type, and they can be delivered with adjuvants.
The era of COVID-19 has brought to the forefront mRNA-based vaccines. At present, lipid nanoparticles (LNPs) are among the most common vectors for in vivo RNA delivery. In general, LNPs a composed of a lipid bilayer shell surrounding an aqueous core. The bilayer shell is created using different lipids; however, other structures have been reported. The majority of LNP formulations utilize cationic lipids to aid in the complexation of negatively charged RNA, although anionic and neutral formulations have also been used historically. Several studies have indicated that cationic lipids that bear a permanent positive charge have higher toxicity while being less efficient. Significant research into the potency of LNPs has led to the development of new, ionizable lipids lipid-like materials.
Under physiological pH conditions, lipids and lipidoids comprise amine groups that maintain a neutral or mildly cationic surface charge, reducing nonspecific lipid-protein interactions. This also facilitates oligonucleotide release in the cytosol. In the endosome, it is suggested that the amine groups are ionized upon acidification aiding in the induction of hexagonal phase structures, thus disrupting the late endosomes membranes, which, in turn, enables endosomal escape and cellular uptake of mRNA into the cytoplasm.
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