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Cytotoxicities of cytosine deaminase and herpes simplex virus thymidine kinase genes in melanoma cells are not affected by the promoter strength

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Abstract

The right choice of regulatory elements (promoters and enhancers) is essential for the preparation within cancer cells of the therapeutic genetic constructs aimed at the gene-programmed enzymatic transformation of non-toxic prodrugs into toxins. It is generally accepted that the efficiency of gene therapy constructions is dependent, in particular, on the strength of promoters regulating the expression of therapeutic genes. Using melanoma-specific promoters and gene enhancers of human melanoma inhibitory activity and mouse tyrosinase and therapeutic genes, namely, HSVtk encoding herpes simplex virus thymidine kinase and FCU1 encoding cytosine deaminase/uracil phosphoribosyltransferase hybrid protein gene, we demonstrated that the promoter strength was not critical for the development of cytotoxic effects. The cytotoxic activity of these genes was shown to be influenced by the concentration of the prodrug added.

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Abbreviations

HSVtk :

herpes simplex virus thymidine kinase gene

FCU1 :

cytosine deaminase/uracil phosphoribosyltransferase hybrid protein gene

CMV:

cytomegalovirus

Luc:

luciferase

MIA :

human melanoma inhibitory activity gene

Tyr :

mouse tyrosinase gene, enhTyr, mouse tyrosinase enhancer gene

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Authors and Affiliations

  1. Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, ul. Miklukho-Maklaya 16/10, Moscow, 117997, Russia

    I. V. Alekseenko, D. V. Kuzmin, V. V. Pleshkan, M. V. Zinovyeva & E. D. Sverdlov

  2. Institute of Molecular Genetics, Russian Academy of Sciences, pl. Kurchatova 2, Moscow, 123182, Russia

    I. V. Alekseenko, V. V. Pleshkan & E. D. Sverdlov

Authors
  1. I. V. Alekseenko
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  2. D. V. Kuzmin
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  3. V. V. Pleshkan
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  4. M. V. Zinovyeva
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  5. E. D. Sverdlov
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Corresponding author

Correspondence to M. V. Zinovyeva.

Additional information

Original Russian Text © I.V. Alekseenko, D.V. Kuzmin, V.V. Pleshkan, M.V. Zinovyeva, E.D. Sverdlov, 2013, published in Bioorganicheskaya Khimiya, 2013, Vol. 39, No. 6, pp. 745–748.

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Alekseenko, I.V., Kuzmin, D.V., Pleshkan, V.V. et al. Cytotoxicities of cytosine deaminase and herpes simplex virus thymidine kinase genes in melanoma cells are not affected by the promoter strength. Russ J Bioorg Chem 39, 665–667 (2013). https://doi.org/10.1134/S1068162013060010

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  • DOI: https://doi.org/10.1134/S1068162013060010

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