有效的mRNA疫苗的特征在于高蛋白（=抗原）表达和低先天免疫原性。
核苷修饰可以影响这些特征，如Kariko等人的开创性工作所示。[1-3]。特别地，N1-甲基假尿苷修饰的mRNA（Andries et al. ）在细胞培养实验中显示出显著增强的蛋白表达以及低免疫原性。
由Pfizer-BioNTech和Moderna开发的COVID-19 mRNA疫苗证明了N1-甲基假尿苷修饰在mRNA疫苗开发中的优异效用，由此在两种mRNA疫苗中尿苷被N1-甲基假尿苷完全取代[6-9]。通过T7 RNA聚合酶介导的体外转录，通过酶促掺入相应的三磷酸N1-甲基假-UTP来制备N1
我们的N1-Methylpseudo-UTP产品组合：
mRNA产量（mL至多升规模）：
| 目录号 | 产品名称 | 规格 |
|---|---|---|
| NU-890-THR | N1-Methylpseudo-UTP，钠盐 | 纯度（HPLC）：>/= 99% 鉴别（MS）：符合规定（阳性和/或阴性模式） 浓度（UV/维斯）：100 - 105 mM pH值：7.5 +/- 0.25其他检测：功能性（T7 IVT）、DNA酶/&RNA酶污染（FRET）、蛋白酶污染（UV-Vis）和内毒素（LAL检测）无动物源性起始物料生产 |
Research & Development:
| 目录号 | 产品名称 | 规格 |
|---|---|---|
| NU-890-S/L | N1-甲基假UTP， 钠盐 | 纯度（HPLC）：>/= 95% 鉴别（MS）：符合规定（阳性和/或阴性模式） 浓度：100 - 110 mM pH值：7.5 +/- 0.5 |
| RNT-107-S/L | HighYield T7 mRNA合成试剂盒 （me 1 μ g-UTP） | 生产100 - 130 µg未加帽的N1-甲基假尿苷修饰的RNA* |
| RNT-115-S/L | HighYield T7 ARCA mRNA合成试剂盒 （me 1 μ g-UTP） | 生产30 - 50 µg ARCA加帽的N1-甲基假尿苷修饰的RNA* |
* 标准反应：1 µg T7 DNA对照模板，1400 nt RNA转录物，37 ℃孵育30 min。
参考文献：
[1] Karikó et al. (2005) Suppression of RNA Recognition by Toll-like Receptors: The Impact of Nucleoside Modification and the Evolutionary Origin of RNA. Immunity 23 (2):165.
[2] Karikó et al. (2008) Incorporation of Pseudouridine yields superior nonimmunogenic vector with increased translational capacity and biological stability. Molecular Therapy 16 (11):1833.
[3] Anderson et al. (2011) Nucleoside modifications in RNA limit activation of 2’-5’-oligoadenylate synthetase and increase resistance to cleavage by RNase L. Nucleic Acids Research 39 (21):9329.
[4] Andries et al. (2015) N1-Methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice. J. Controlled Release 217:337.
[5] Svitkin et al. (2017) N1-methyl-pseudouridine in mRNA Enhances Translation through eIFalpha-dependent and Independent Mechanism by Increasing Ribosome Density. Nucleic Acids Res. 45:6023.
[6] Morais et al. (2021) The Critical Contribution of Pseudourdine to mRNA COVID-19 Vaccines. Frontiers in Cell and Developmental Biology 9:1.
[7] Nance et al. (2021) Modifications in an Emergency: The Role of N1-Methylpseudouridine in COVID-19 vaccines. ACS Cent. Sci. 7 (5):748.
[8] Chaudhary et al. (2021) mRNA vaccines for infectious diseases: principles, delivery and clinical translation. Nature Reviews Drug Discovery 20:817.
[9] Dolgin (2021) CureVac COVID Vaccine Let-Down Spotlights mRNA Design Challenges. Nature 594:483.
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