Under the background of rapid development of modern medicine and biotechnology, the rise of mRNA vaccine technology not only marks a new era of vaccine research and development, but also provides a brand new idea and method for the prevention and treatment of infectious diseases. mRNA vaccine, as a kind of nucleic acid-based vaccine, has the significant advantage of not integrating into the host genome compared to DNA vaccine, reducing the risk of gene mutation. In addition, compared with the widely used protein vaccines, the cell-free production of mRNA vaccines not only accelerates the development cycle of vaccines, but also improves the production efficiency and the possibility of large-scale production. mRNA vaccines can encode a variety of antigens to adapt to a diversity of microorganisms or viral variants, and at the same time, combine the dual functions of encoding antigens and adjuvants to effectively stimulate immune responses.

The core of mRNA vaccine technology is its ability to respond rapidly to emerging pathogens. The successful application of mRNA vaccines, such as the Pfizer-BioNTech vaccine and Moderna vaccine, in new crown epidemics has not only demonstrated their great potential in emergency response, but also verified their effectiveness and safety in mass immunization. However, although mRNA vaccine technology has shown great potential and advantages in new crown epidemics, the optimization of its stability and immunogenicity, as well as the improvement of its safety, remain key challenges in the development of the technology. For example, the optimization of the 5'-cap, 5'-untranslated region (5'-UTR), open reading frame (ORF), 3'-untranslated region (3'-UTR), and poly(adenylate) tail [p-adenylate) of mRNAs is a key challenge for the development of the technology. The precise regulation of open reading frame (ORF), 3'-untranslated region (3'-UTR) and poly-adenylated tail (poly(A)) sequences is the key to enhance the stability and expression efficiency of mRNA. In addition, improving the efficiency of the mRNA delivery system is also crucial to realize its clinical applications. For example, lipid nanoparticles (LNPs), as an effective delivery system, have shown excellent delivery effects in several clinical trials.

Globally, mRNA vaccine development is facing different trends and challenges. The successful application of mRNA vaccines in the Xinguang epidemic has provided a new direction for global vaccine research and development. In the future, mRNA vaccine technology is expected to play a role in the prevention and treatment of various diseases such as cancer and acquired immunodeficiency syndrome. Meanwhile, technological innovations, such as improving the temperature stability of mRNA vaccines, will simplify the storage and transportation conditions and make the vaccines more accessible.

In this paper, we review the recent advances in sequence optimization strategies and delivery systems of mRNA vaccines, as well as their applications in the prevention and treatment of infectious diseases, with the aim of providing references for future vaccine research and applications.

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