Optimization and Evaluation of a Dendritic Cell-targeting Strategy based on Lipid Nanoparticle-mRNAVaccine

Lingyu Wang

doi:10.54097/59f16038

Authors

Lingyu Wang

DOI:

https://doi.org/10.54097/59f16038

Keywords:

mRNA Vaccine, DC Cell Targeting, Mannose Receptor, Cancer Prevention

Abstract

Infectious diseases and cancer are major public health challenges facing the world today, posing a persistent threat to human health. Vaccines based on messenger RNA (mRNA) technology have demonstrated great potential in disease prevention and control due to their efficient delivery and immune activation capabilities. Although the use of lipid nanoparticles (LNPs) has significantly improved the intracellular delivery efficiency of mRNA, issues such as insufficient mRNA stability, poor targeting, limited expression levels, and cumulative liver toxicity still retain. This study proposes a dual optimization strategy for mRNA vaccines: by optimizing the untranslated region (UTR) sequence, introducing a 5’ cap structure, and a segmented poly(A) tail at the 3’ end, significantly enhancing mRNA stability and translation efficiency. And we innovatively employed mannose-modified polyethylene glycol (PEG)-coated lipid nanoparticles, leveraging mannose receptors on dendritic cells (DCs) to achieve active targeted delivery. This study effectively enhanced the targeting transfection efficiency of LNP/mRNA vaccines for dendritic cells, providing a new idea for the optimization strategy of LNP- based mRNA vaccines and having important application reference value for promoting tumor immunotherapy and the prevention and control of infectious diseases.

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