Abstract
Messenger ribonucleic acid (mRNA)-based drugs, notably mRNA vaccines, have been widely proven as a promising treatment strategy in immune therapeutics. The extraordinary advantages associated with mRNA vaccines, including their high efficacy, a relatively low severity of side effects, and low attainment costs, have enabled them to become prevalent in pre-clinical and clinical trials against various infectious diseases and cancers. Recent technological advancements have alleviated some issues that hinder mRNA vaccine development, such as low efficiency that exist in both gene translation and in vivo deliveries. mRNA immunogenicity can also be greatly adjusted as a result of upgraded technologies. In this review, we have summarized details regarding the optimization of mRNA vaccines, and the underlying biological mechanisms of this form of vaccines. Applications of mRNA vaccines in some infectious diseases and cancers are introduced. It also includes our prospections for mRNA vaccine applications in diseases caused by bacterial pathogens, such as tuberculosis. At the same time, some suggestions for future mRNA vaccine development about storage methods, safety concerns, and personalized vaccine synthesis can be found in the context.
Highlights
MRNA, an intermediate hereditary substance in the central dogma, was first discovered in 1961 by Brenner et al [1]
Phosphorothioate modifying based on anti-reverse cap analogs (ARCA), for example, would enhance the translation efficiency of Messenger ribonucleic acid (mRNA) by increasing its affinity for eukaryotic translation initiation factor 4E (eIF4E), and has the ability to decrease the susceptibility to decapping enzymes so as to improve the mRNA stability [35,36,37]
The ionizable cationic lipid can promote the autonomous aggregation of mRNAs to form a ~100 nm particle and release mRNAs in the cytoplasm through ionization; natural phospholipids support the nanoparticles to form a lipid bilayer structure; cholesterol is used as a stabilizer to increase lipid nanoparticles (LNP) stability; and polyethylene glycol (PEG) can extend the half-life of LNP complex [21,133]. mRNA is carried in the core of LNP which can be protected from degradation, and the lipophilicity property of LNP material allows the mRNA delivery complex to fuse with the host cell membrane and deliver mRNA into the cells by endocytosis [19,119]
Summary
MRNA, an intermediate hereditary substance in the central dogma, was first discovered in 1961 by Brenner et al [1]. Phosphorothioate modifying based on ARCA, for example, would enhance the translation efficiency of mRNA by increasing its affinity for eIF4E, and has the ability to decrease the susceptibility to decapping enzymes so as to improve the mRNA stability [35,36,37]. It has been indicated that since the lengths of Poly (A) sequences required for high translation efficiency mRNA in various types of cells are different, adjustments should be made to optimize the translation efficiency of mRNA
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