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Untranslated Region Sequences and the Efficacy of mRNA Vaccines against Tuberculosis.
Reshetnikov, Vasiliy; Terenin, Ilya; Shepelkova, Galina; Yeremeev, Vladimir; Kolmykov, Semyon; Nagornykh, Maxim; Kolosova, Elena; Sokolova, Tatiana; Zaborova, Olga; Kukushkin, Ivan; Kazakova, Alisa; Kunyk, Dmitry; Kirshina, Anna; Vasileva, Olga; Seregina, Kristina; Pateev, Ildus; Kolpakov, Fedor; Ivanov, Roman.
Afiliación
  • Reshetnikov V; Translational Medicine Research Center, Sirius University of Science and Technology, 354340 Sochi, Russia.
  • Terenin I; Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia.
  • Shepelkova G; Translational Medicine Research Center, Sirius University of Science and Technology, 354340 Sochi, Russia.
  • Yeremeev V; Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, 119991 Moscow, Russia.
  • Kolmykov S; Central Tuberculosis Research Institute, 107564 Moscow, Russia.
  • Nagornykh M; Central Tuberculosis Research Institute, 107564 Moscow, Russia.
  • Kolosova E; Translational Medicine Research Center, Sirius University of Science and Technology, 354340 Sochi, Russia.
  • Sokolova T; Translational Medicine Research Center, Sirius University of Science and Technology, 354340 Sochi, Russia.
  • Zaborova O; Translational Medicine Research Center, Sirius University of Science and Technology, 354340 Sochi, Russia.
  • Kukushkin I; Translational Medicine Research Center, Sirius University of Science and Technology, 354340 Sochi, Russia.
  • Kazakova A; Translational Medicine Research Center, Sirius University of Science and Technology, 354340 Sochi, Russia.
  • Kunyk D; Translational Medicine Research Center, Sirius University of Science and Technology, 354340 Sochi, Russia.
  • Kirshina A; Translational Medicine Research Center, Sirius University of Science and Technology, 354340 Sochi, Russia.
  • Vasileva O; Translational Medicine Research Center, Sirius University of Science and Technology, 354340 Sochi, Russia.
  • Seregina K; Translational Medicine Research Center, Sirius University of Science and Technology, 354340 Sochi, Russia.
  • Pateev I; Translational Medicine Research Center, Sirius University of Science and Technology, 354340 Sochi, Russia.
  • Kolpakov F; Translational Medicine Research Center, Sirius University of Science and Technology, 354340 Sochi, Russia.
  • Ivanov R; Translational Medicine Research Center, Sirius University of Science and Technology, 354340 Sochi, Russia.
Int J Mol Sci ; 25(2)2024 Jan 10.
Article en En | MEDLINE | ID: mdl-38255961
ABSTRACT
mRNA vaccines have been shown to be effective in combating the COVID-19 pandemic. The amount of research on the use of mRNAs as preventive and therapeutic modalities has undergone explosive growth in the last few years. Nonetheless, the issue of the stability of mRNA molecules and their translation efficiency remains incompletely resolved. These characteristics of mRNA directly affect the expression level of a desired protein. Regulatory elements of RNA-5' and 3' untranslated regions (UTRs)-are responsible for translation efficiency. An optimal combination of the regulatory sequences allows mRNA to significantly increase the target protein's expression. We assessed the translation efficiency of mRNA encoding of firefly luciferase with various 5' and 3'UTRs in vitro on cell lines DC2.4 and THP1. We found that mRNAs containing 5'UTR sequences from eukaryotic genes HBB, HSPA1A, Rabb, or H4C2, or from the adenoviral leader sequence TPL, resulted in higher levels of luciferase bioluminescence 4 h after transfection of DC2.4 cells as compared with 5'UTR sequences used in vaccines mRNA-1273 and BNT162b2 from Moderna and BioNTech. mRNA containing TPL as the 5'UTR also showed higher efficiency (as compared with the 5'UTR from Moderna) at generating a T-cell response in mice immunized with mRNA vaccines encoding a multiepitope antigen. By contrast, no effects of various 5'UTRs and 3'UTRs were detectable in THP1 cells, suggesting that the observed effects are cell type specific. Further analyses enabled us to identify potential cell type-specific RNA-binding proteins that differ in landing sites within mRNAs with various 5'UTRs and 3'UTRs. Taken together, our data indicate high translation efficiency of TPL as a 5'UTR, according to experiments on DC2.4 cells and C57BL/6 mice.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis / Antígenos de Grupos Sanguíneos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Rusia Pais de publicación: Suiza
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Tuberculosis / Antígenos de Grupos Sanguíneos Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Int J Mol Sci Año: 2024 Tipo del documento: Article País de afiliación: Rusia Pais de publicación: Suiza