Development of mRNA Vaccines/Therapeutics and Their Delivery System

Abstract

The rapid development of mRNA vaccines has contributed to the management of the current coronavirus disease 2019 (COVID-19) pandemic, suggesting that this technology may be used to manage future outbreaks of infectious diseases. Because the antigens targeted by mRNA vaccines can be easily altered by simply changing the sequence present in the coding region of mRNA structures, it is more appropriate to develop vaccines, especially during rapidly developing outbreaks of infectious diseases. In addition to allowing rapid development, mRNA vaccines have great potential in inducing successful antigen-specific immunity by expressing target antigens in cells and simultaneously triggering immune responses. Indeed, the two COVID-19 mRNA vaccines approved by the U.S. Food and Drug Administration have shown significant efficacy in preventing infections. The ability of mRNAs to produce target proteins that are defective in specific diseases has enabled the development of options to treat intractable diseases. Clinical applications of mRNA vaccines/therapeutics require strategies to safely deliver the RNA molecules into targeted cells. The present review summarizes current knowledge about mRNA vaccines/ therapeutics, their clinical applications, and their delivery strategies.

Keywords: RNA delivery; RNA therapeutics; mRNA therapeutics; mRNA vaccine.

Fig. 1. Mechanism of action of mRNA vaccines.

mRNA vaccines to prevent COVID-19 were developed by encapsulating chemically modified mRNAs in lipid nanoparticles. After endocytosis, mRNA can be delivered into the cytoplasm, resulting in the induction of antigen expression. The antigens translated by mRNA vaccines can induce both cell-mediated and antibody-mediated immunity. MHC, major histocompatibility complex; TAP, The transporter associated with antigen processing. Created with BioRender.com.

Fig. 2. mRNA therapeutics/vaccines for inducing protein expression.

Conventional types of mRNA therapeutics includes 5′cap, 5′UTR, open reading frame (ORF), 3′UTR, and poly(A), which induce cap-dependent translation following transfection into delivered cells, resulting in protein expression. During the development of mRNA therapeutics and vaccines, the ORF region was designed to express therapeutic proteins and antigens, respectively. Created with BioRender.com.

Fig. 3. Strategies for RNA delivery.

Encapsulation of RNA therapeutic agents by various nanomaterials, including lipoplexes, polyplexes, polymer nanoparticles (polymer NP), and lipid nanoparticles (LNP), protecting the RNAs and delivering them to desired cells. By chemical conjugation with various targeting ligands, these RNAs, especially short RNAs such as siRNAs and miRNAs, can be delivered into cells. Created with BioRender.com.