mRNA vaccines in disease prevention and treatment

Abstract

mRNA vaccines have emerged as highly effective strategies in the prophylaxis and treatment of diseases, thanks largely although not totally to their extraordinary performance in recent years against the worldwide plague COVID-19. The huge superiority of mRNA vaccines regarding their efficacy, safety, and large-scale manufacture encourages pharmaceutical industries and biotechnology companies to expand their application to a diverse array of diseases, despite the nonnegligible problems in design, fabrication, and mode of administration. This review delves into the technical underpinnings of mRNA vaccines, covering mRNA design, synthesis, delivery, and adjuvant technologies. Moreover, this review presents a systematic retrospective analysis in a logical and well-organized manner, shedding light on representative mRNA vaccines employed in various diseases. The scope extends across infectious diseases, cancers, immunological diseases, tissue damages, and rare diseases, showcasing the versatility and potential of mRNA vaccines in diverse therapeutic areas. Furthermore, this review engages in a prospective discussion regarding the current challenge and potential direction for the advancement and utilization of mRNA vaccines. Overall, this comprehensive review serves as a valuable resource for researchers, clinicians, and industry professionals, providing a comprehensive understanding of the technical aspects, historical context, and future prospects of mRNA vaccines in the fight against various diseases.

Fig. 1

Dual effects of mRNA vaccine on immune activation. mRNA vaccines induce both innate and adaptive immunity. Endocytosis of exogeneous mRNA by antigen presenting cells is sensed by TLR3 and TLR7/8 in the endosomes as well as RIG-1, NOD2, LGP2, and MDA-5 in the cytosol, inducing strong IFN-I responses, then triggering proinflammatory cytokine production, thereby activating innate immunity (left). mRNA-encoded protein is released out of the cell to activate B cells, while mRNA-encoded or re-endocytosed proteins are degraded as peptides in the proteasome to be presented on MHC-I or MHC-II molecules to activate CD4⁺ and CD8⁺ T cells, cocontributing to adaptive immunity activation (right). This figure is created using Adobe Illustrator and is inspired by these two papers^,

Fig. 2

Pipeline for the development of mRNA vaccines. The development of mRNA vaccines includes a series of steps, including sequencing design, in vitro transcription, purification, nanoprecipitation, and filtration. This figure is created using Adobe Illustrator and refers to this paper

Fig. 3

Landscape of mRNA vaccines in infectious diseases. mRNA vaccines have been developed against multiple infectious diseases to date, including severe acute respiratory syndrome coronavirus 2, zika virus, human immunodeficiency virus, influenza virus, cytomegalovirus, respiratory syncytial virus, varicella-zoster virus, and rabies virus. This figure is created using Adobe Illustrator and integrates the current literature-based knowledge

Fig. 4

Landscape of mRNA vaccines in cancers. mRNA vaccines have been developed against multiple cancers to date, including melanoma, brain cancer, non-small cell lung cancer, ovarian cancer, prostate cancer, blood system cancer, digestive system cancer, and breast cancer. This figure is created using Adobe Illustrator and integrates the current literature-based knowledge