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Messenger RNA (mRNA) vaccines have shown great preventive potential in response to the novel coronavirus (COVID-19) pandemic. The lipid nanoparticle (LNP), as a non-viral vector with good safety and potency factors, is applied to mRNA delivery in the clinic. Among the recently FDA-approved SARS-CoV-2 mRNA vaccines, lipid-based nanoparticles have been shown to be well-suited to antigen presentation and enhanced immune stimulation to elicit potent humoral and cellular immune responses. However, a design strategy for optimal mRNA-LNP vaccines has not been fully elaborated. In this review, we comprehensively and systematically discuss the research strategies for mRNA-LNP vaccines against COVID-19, including antigen and lipid carrier selection, vaccine preparation, quality control, and stability. Meanwhile, we also discuss the potential development directions for mRNA–LNP vaccines in the future. We also conduct an in-depth review of those technologies and scientific insights in regard to the mRNA-LNP field.
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