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DOI: 10.24075/brsmu.2024.048

ORIGINAL RESEARCH

Production and biological activity of the exogenous mRNA encoding human MxA protein

Plotnikova MA1, Bobkov DE1,2, Klotchenko SA1
About authors

1 Smorodintsev Research Institute of Influenza of the Ministry of Health of the Russian Federation, St. Petersburg, Russia

2 Institute of Cytology, Russian Academy of Science, St. Petersburg, Russia

Correspondence should be addressed: Sergey A. Klotchenko
Professora Popova, 15/17, St. Petersburg, 197022, Russia; ur.liam@kitafsof

About paper

Funding: the study was supported by the Russian Science Foundation, Agreement No. 23-25-00433, project title: “Assessment of antiviral effect of the mRNA encoding human MxA protein” (manager M.A. Plotnikova), https://rscf.ru/project/23-25-00433/

Author contribution: Plotnikova MA — study design, experimental procedure, analysis of the results, statistical processing, manuscript writing; Bobkov DE — confocal microscopy examination; Klotchenko SA — production and characterization of the exogenous mRNA preparations, manuscript editing.

Received: 2024-09-30 Accepted: 2024-10-22 Published online: 2024-10-30
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  1. Liao S, Gao S. MxA: a broadly acting effector of interferon-induced human innate immunity. Visualized Cancer Medicine. 2022; 3: 2. Available from: https://doi.org/10.1051/vcm/2022002.
  2. Verhelst J, Hulpiau P, Saelens X. Mx proteins: antiviral gatekeepers that restrain the uninvited. Microbiology and Molecular Biology Reviews. 2013; 77 (4): 551–66. Available from: https://doi.org/10.1128/mmbr.00024-13.
  3. Haller O, Kochs G. Interferon–induced mx proteins: dynamin–like GTPases with antiviral activity. Traffic. 2002; 3 (10): 710–7. Available from: https://doi.org/10.1034/j.1600-0854.2002.31003.x.
  4. Zürcher T, Pavlovic J, Staeheli P. Mechanism of human MxA protein action: variants with changed antiviral properties. The EMBO Journal. 1992; 11 (4): 1657–61. Available from: https://doi.org/10.1002/j.1460-2075.1992.tb05212.x.
  5. Johannes L, et al. Antiviral determinants of rat Mx GTPases map to the carboxy-terminal half. Journal of virology. 1997; 71 (12): 9792–5. Available from: https://doi.org/10.1128/jvi.71.12.9792-9795.1997.
  6. Jung HE, Oh JE, Lee HK. Cell-penetrating Mx1 enhances anti-viral resistance against mucosal influenza viral infection. Viruses. 2019; 11 (2): 109. Available from: https://doi.org/10.3390/v11020109.
  7. Sistigu A, et al. Cancer cell–autonomous contribution of type I interferon signaling to the efficacy of chemotherapy. Nature medicine. 2014; 20 (11): 1301–9. Available from: https://doi.org/10.1038/nm.3708.
  8. Kim YA, et al. MxA expression is associated with tumor-infiltrating lymphocytes and is a prognostic factor in triple-negative breast cancer. Breast cancer research and treatment. 2016; 156: 597–606. Available from: https://doi.org/10.1007/s10549-016-3786-z.
  9. Klotchenko S. A. et al. Comparative analysis of MxA, OAS1, PKR gene expression levels in leukocytes of patients with influenza and coronavirus infection. Medical academic journal. 2023; 23 (3): 65– 75. Available from: https://doi.org/10.17816/MAJ623374.
  10. База данных NCBI, доступно по ссылке: https://www.ncbi.nlm. nih.gov/nuccore/.
  11. Noguchi S, et al. MxA transcripts with distinct first exons and modulation of gene expression levels by single-nucleotide polymorphisms in human bronchial epithelial cells. Immunogenetics. 2013; 65: 107–14. Available from: https://doi.org/10.1007/s00251-012-0663-8.
  12. Tazi-Ahnini R, et al. Structure and polymorphism of the human gene for the interferon-induced p78 protein (MX1): evidence of association with alopecia areata in the Down syndrome region. Human genetics. 2000; 106: 639–45. Available from: https://doi.org/10.1007/s004390000318.
  13. Elroy-Stein O, Fuerst TR, Moss B. Cap-independent translation of mRNA conferred by encephalomyocarditis virus 5'sequence improves the performance of the vaccinia virus/bacteriophage T7 hybrid expression system. Proceedings of the National Academy of Sciences. 1989; 86 16: 6126–30. Available from: https://doi.org/10.1073/pnas.86.16.6126.
  14. Bochkov YA, Palmenberg AC. Translational efficiency of EMCV IRES in bicistronic vectors is dependent upon IRES sequence and gene location. Biotechniques. 2006; 41 (3): 283–92. Available from: https://doi.org/10.2144/000112243.
  15. Kariko K, Weissman D. Naturally occurring nucleoside modifications suppress the immunostimulatory activity of RNA: implication for therapeutic RNA development. Current Opinion in Drug Discovery and Development. 2007; 10 (5): 523. PMID: 17786850.
  16. Karikó K, et al. Incorporation of pseudouridine into mRNA yields superior nonimmunogenic vector with increased translational capacity and biological stability. Molecular therapy. 2008; 16 11: 1833–40. Available from: https://doi.org/10.1038/mt.2008.200.
  17. Weissman D. mRNA transcript therapy. Expert review of vaccines. 2015; 14 (2): 265–81. Available from: https://doi.org/10.1586/14 760584.2015.973859.
  18. von Niessen AGO, et al. Improving mRNA-based therapeutic gene delivery by expression-augmenting 3′ UTRs identified by cellular library screening. Molecular Therapy. 2019; 27 (4): 824–36. Available from: https://doi.org/10.1016/j.ymthe.2018.12.011.
  19. Xue S, et al. RNA regulons in Hox 5′ UTRs confer ribosome specificity to gene regulation. Nature. 2015; 517 (7532): 33–38. Available from: https://doi.org/10.1038/nature14010.
  20. Koch A, et al. Quantifying the dynamics of IRES and cap translation with single-molecule resolution in live cells. Nature structural & molecular biology. 2020; 27 (12): 1095–104. Available from: https://doi.org/10.1038/s41594-020-0504-7.
  21. Haller O, Kochs G. Mx genes: host determinants controlling influenza virus infection and trans-species transmission. Human genetics. 2020; 139 (6): 695–705. Available from: https://doi.org/10.1007/s00439-019-02092-8.
  22. Kawai T, Akira S. The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. Nature immunology. 2010; 11 (5): 373–84. Available from: https://doi.org/10.1038/ni.1863.