核苷修饰：IVT mRNA 药物安全有效的关键因素

赛默飞应用解决方案

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[1] The Nobel Prize in Physiology or Medicine 2023. https://www.nobelprize.org/prizes/medicine/2023/summary/

[2] 侯书婷, 于传飞, 王兰, 王军志. 体外转录mRNA药物的技术进展和应用前景[J]. 药学学报, 2023, 58(8): 2047-2058. DOI: 10.16438/j.0513-4870.2023-0201

[3] Karikó, K., Buckstein, M., Ni, H. and Weissman, D. Suppression of RNA Recognition by Toll-like Receptors: The impact of nucleoside modification and the evolutionary origin of RNA. Immunity 23, 165–175 (2005).

[4] Karikó, K., Muramatsu, H., Welsh, F.A., Ludwig, J., Kato, H., Akira, S. and Weissman, D. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Mol Ther 16, 1833–1840 (2008).

[5] Anderson, B.R., Muramatsu, H., Nallagatla, S.R., Bevilacqua, P.C., Sansing, L.H., Weissman, D. and Karikó, K. Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation. Nucleic Acids Res. 38, 5884–5892 (2010).

[6] Overview of In Vitro Transcription. https://www.thermofisher.cn/cn/zh/home/industrial/pharma-biopharma/nucleic-acid-therapeutic-development-solutions/mrna-research/overview-in-vitro-transcription.html

[7] Andries O, Mc Cafferty S, De Smedt SC, Weiss R, Sanders NN, Kitada T. N(1)-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice. J Control Release. 2015 Nov 10;217:337-44. doi: 10.1016/j.jconrel.2015.08.051. Epub 2015 Sep 3. PMID: 26342664.

[8] Morais P, Adachi H, Yu YT. The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines. Front Cell Dev Biol. 2021 Nov 4; 9:789427. doi: 10.3389/fcell.2021.789427. PMID: 34805188; PMCID: PMC8600071.

[9] Mulroney, T.E., P?yry, T., Yam-Puc, J.C. et al. N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting. Nature 625, 189–194 (2024). https://doi.org/10.1038/s41586-023-06800-3

[10] Ziegenhals T, Frieling R, Wolf P, G?bel K, Koch S, Lohmann M, Baiersd?rfer M, Fesser S, Sahin U, Kuhn AN. Formation of dsRNA by-products during in vitro transcription can be reduced by using low steady-state levels of UTP. Front Mol Biosci. 2023 Dec 11;10:1291045. doi: 10.3389/fmolb.2023.1291045.

[11] Welbourne EN, Loveday KA, Nair A, Nourafkan E, Qu J, Cook K, Kis Z, Dickman MJ. Anion exchange HPLC monitoring of mRNA in vitro transcription reactions to support mRNA manufacturing process development. Front Mol Biosci. 2024 Mar 7;11:1250833. doi: 10.3389/fmolb.2024.1250833. PMID: 38516194; PMCID: PMC10955092.

[12] Acclaim C30 column - Thermo ScientificTM AcclaimTM C30 columns provide unique selectivity and superior separations of hydrophobic, structurally related analytes.