Yang Tongren, Li Chunhui, Wang Xiaoxia, Zhao Deyao, Zhang Mengjie, Cao Huiqing, Liang Zicai, Xiao Haihua, Liang Xing-Jie, Weng Yuhua, Huang Yuanyu
School of Life Science, Advanced Research Institute of Multidisciplinary Science, Institute of Engineering Medicine, Key Laboratory of Molecular Medicine and Biotherapy, Beijing Institute of Technology, Beijing, 100081, China.
Institute of Molecular Medicine, Peking University, Beijing, 100871, China.
Bioact Mater. 2020 Jul 13;5(4):1053-1061. doi: 10.1016/j.bioactmat.2020.07.003. eCollection 2020 Dec.
mRNA is a novel class of therapeutic modality that holds great promise in vaccination, protein replacement therapy, cancer immunotherapy, immune cell engineering However, optimization of mRNA molecules and efficient delivery are quite important but challenging for its broad application. Here we present an ionizable lipid nanoparticle (iLNP) based on iBL0713 lipid for and expression of desired proteins using codon-optimized mRNAs. mRNAs encoding luciferase or erythropoietin (EPO) were prepared by transcription and formulated with proposed iLNP, to form iLP171/mRNA formulations. It was revealed that both luciferase and EPO proteins were successfully expressed by human hepatocellular carcinoma cells and hepatocytes. The maximum amount of protein expression was found at 6 h post-administration. The expression efficiency of EPO with codon-optimized mRNA was significantly higher than that of unoptimized mRNA. Moreover, no toxicity or immunogenicity was observed for these mRNA formulations. Therefore, our study provides a useful and promising platform for mRNA therapeutic development.
信使核糖核酸（mRNA）是一种新型治疗方式，在疫苗接种、蛋白质替代疗法、癌症免疫疗法、免疫细胞工程等方面具有巨大潜力。然而，mRNA分子的优化和有效递送对于其广泛应用而言非常重要但具有挑战性。在此，我们展示了一种基于iBL0713脂质的可电离脂质纳米颗粒（iLNP），用于使用密码子优化的mRNA表达所需蛋白质。通过体外转录制备编码荧光素酶或促红细胞生成素（EPO）的mRNA，并与所提出的iLNP一起配制，形成iLP171/mRNA制剂。结果显示，人肝癌细胞和肝细胞均成功表达了荧光素酶和EPO蛋白。在给药后6小时发现蛋白质表达量最高。密码子优化的mRNA的EPO表达效率显著高于未优化的mRNA。此外，这些mRNA制剂未观察到毒性或免疫原性。因此，我们的研究为mRNA治疗开发提供了一个有用且有前景的平台。
