Journal of Vaccine Research 2024, Vol.14, No.3, 95-106 http://medscipublisher.com/index.php/jvr 96 2 Historical Background of mRNA Vaccine Development 2.1 Early research and conceptualization The concept of using messenger RNA (mRNA) for therapeutic purposes dates back several decades, with early research exploring its potential as a versatile and efficient platform for protein expression. Initial studies in the 1990s demonstrated that mRNA could be used to produce proteins in vitro and in vivo, sparking interest in its potential applications for vaccine development and gene therapy (Pardi et al., 2020). Researchers faced significant challenges, including the inherent instability of mRNA and its rapid degradation by nucleases, which limited its practical use. However, advancements in nucleotide modification and the development of more stable mRNA constructs helped overcome these initial hurdles (Gote et al., 2023). 2.2 Technological milestones Several key technological milestones marked the evolution of mRNA vaccine development. Figure 1 clearly illustrates the notable progress in mRNA technology in both basic and applied research fields since 1961. These advancements have driven the development of mRNA vaccines and therapeutics, providing an essential historical context and reference for future research. One of the most significant advancements was the development of lipid nanoparticle (LNP) delivery systems. LNPs protect mRNA from degradation and facilitate its delivery into host cells, where it can be translated into the target protein (Hassett et al., 2019). Additionally, the introduction of modified nucleosides in mRNA sequences significantly improved the stability and translation efficiency of mRNA, reducing its immunogenicity and enhancing its therapeutic potential (Jackson et al., 2020). Figure 1 Timeline of key discoveries and advancements in mRNA technology (Adapted from Xu et al., 2020) Image Caption: The green boxes represent discoveries and advancements in the mechanisms of mRNA, while the blue boxes indicate discoveries and advancements in the applications of mRNA drugs. Key technological advancements in mRNA mentioned in the figure include the 5' cap structure, lipid nanoparticles (LNP), and dendritic cells (DCs) research. The timeline also marks significant progress related to the COVID-19 pandemic, highlighting the potential of mRNA technology in addressing global infectious diseases (Adapted from Xu et al., 2020) Another critical milestone was the successful demonstration of mRNA vaccines in preclinical models. Studies showed that mRNA vaccines could induce strong immune responses and provide protection against various infectious diseases, laying the groundwork for further development (Zhang et al., 2019). These advancements culminated in the establishment of scalable manufacturing processes, enabling the rapid production of high-quality mRNA vaccines (Rosa et al., 2021).
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