新型mRNA帽类似物m7GvpppA2-OMeG的合成与生物活性研究
Synthesis and Biological Activity Evaluation of a Novel mRNA Cap Analogue
李忠阳1
作者信息
摘要
帽类似物(Cap Analogs)是一类用于模拟真核细胞mRNA 5'端帽子结构的化合物,它们在mRNA的合成、稳定性、翻译效率以及免疫原性等方面起着重要作用.本研究合成了一种新型mRNA帽类似物m7GvpppA2-OMeG,并通过对其生物活性的研究来探索其潜在的应用价值.通过开展一系列细胞和活体实验发现该帽类似物加帽的mRNA相比市售帽类似物加帽的mRNA具有更高的加帽率、更好的稳定性、更高的翻译效率.进一步利用该新型帽类似物构建的单纯疱疹病毒mRNA疫苗在小鼠体内产生的IgG抗体水平和IFN-γ表达水平分别提高了 2.70倍和2.67倍,显示出该新型帽类似物在mRNA疫苗应用中的潜力.
Abstract
Cap analogs are a class of compounds used to mimic the 5'cap structure of mRNA in eukaryotic cells,playing important roles in mRNA synthesis,stability,translation efficiency,and immunogenicity.In this study,a novel mRNA cap analog m7GvpppA2-OMeG was synthesized and its potential application value was explored through investigation of its biological activity.A series of cellular and in vivo experiments revealed that mRNA capped with this cap analog exhibited higher capping efficiency,better stability,and increased translation efficiency compared to commercially available cap-analog-capped mRNA.Furthermore,the use of this novel cap analog for constructing a HSV mRNA vaccine resulted in 2.70-fold increase in IgG antibody levels and 2.67-fold increase in IFN-γ expression levels in mice,demonstrating the potential of this new cap analog for mRNA vaccine applications.
关键词
帽类似物/体外转录/稳定性/免疫激活/mRNA疫苗Key words
cap analogs/in vitro transcription/stability/immunostimulation/mRNA vaccines引用本文复制引用
出版年
2024
NETL
NSTL
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