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Efficiency of Promoters of Human Genes FAP and CTGF at Organism Level in a Danio rerio Model

The identification of tissue-specific promoters for gene therapeutic constructs is one of the aims of complex tumor therapy. The genes encoding the fibroblast activation protein (FAP) and the connective tissue growth factor (CTGF) can function in tumor-associated stromal cells but are practically in...

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Autores principales: Selina, Polina I., Alekseenko, Irina V., Kurtova, Anastasia I., Pleshkan, Victor V., Voronezhskaya, Elena E., Demidyuk, Ilya V., Kostrov, Sergey V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138699/
https://www.ncbi.nlm.nih.gov/pubmed/37108352
http://dx.doi.org/10.3390/ijms24087192
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author Selina, Polina I.
Alekseenko, Irina V.
Kurtova, Anastasia I.
Pleshkan, Victor V.
Voronezhskaya, Elena E.
Demidyuk, Ilya V.
Kostrov, Sergey V.
author_facet Selina, Polina I.
Alekseenko, Irina V.
Kurtova, Anastasia I.
Pleshkan, Victor V.
Voronezhskaya, Elena E.
Demidyuk, Ilya V.
Kostrov, Sergey V.
author_sort Selina, Polina I.
collection PubMed
description The identification of tissue-specific promoters for gene therapeutic constructs is one of the aims of complex tumor therapy. The genes encoding the fibroblast activation protein (FAP) and the connective tissue growth factor (CTGF) can function in tumor-associated stromal cells but are practically inactive in normal adult cells. Accordingly, the promoters of these genes can be used to develop vectors targeted to the tumor microenvironment. However, the efficiency of these promoters within genetic constructs remains underexplored, particularly, at the organism level. Here, we used the model of Danio rerio embryos to study the efficiency of transient expression of marker genes under the control of promoters of the FAP, CTGF, and immediate early genes of Human cytomegalovirus (CMV). Within 96 h after the injection of vectors, the CTGF and CMV promoters provided similar equal efficiency of reporter protein accumulation. In the case of the FAP promoter, a high level of reporter protein accumulation was observed only in certain zebrafish individuals that were considered developmentally abnormal. Disturbed embryogenesis was the factor of changes in the exogenous FAP promoter function. The data obtained make a significant contribution to understanding the function of the human CTGF and FAP promoters within vectors to assess their potential in gene therapy.
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spelling pubmed-101386992023-04-28 Efficiency of Promoters of Human Genes FAP and CTGF at Organism Level in a Danio rerio Model Selina, Polina I. Alekseenko, Irina V. Kurtova, Anastasia I. Pleshkan, Victor V. Voronezhskaya, Elena E. Demidyuk, Ilya V. Kostrov, Sergey V. Int J Mol Sci Article The identification of tissue-specific promoters for gene therapeutic constructs is one of the aims of complex tumor therapy. The genes encoding the fibroblast activation protein (FAP) and the connective tissue growth factor (CTGF) can function in tumor-associated stromal cells but are practically inactive in normal adult cells. Accordingly, the promoters of these genes can be used to develop vectors targeted to the tumor microenvironment. However, the efficiency of these promoters within genetic constructs remains underexplored, particularly, at the organism level. Here, we used the model of Danio rerio embryos to study the efficiency of transient expression of marker genes under the control of promoters of the FAP, CTGF, and immediate early genes of Human cytomegalovirus (CMV). Within 96 h after the injection of vectors, the CTGF and CMV promoters provided similar equal efficiency of reporter protein accumulation. In the case of the FAP promoter, a high level of reporter protein accumulation was observed only in certain zebrafish individuals that were considered developmentally abnormal. Disturbed embryogenesis was the factor of changes in the exogenous FAP promoter function. The data obtained make a significant contribution to understanding the function of the human CTGF and FAP promoters within vectors to assess their potential in gene therapy. MDPI 2023-04-13 /pmc/articles/PMC10138699/ /pubmed/37108352 http://dx.doi.org/10.3390/ijms24087192 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Selina, Polina I.
Alekseenko, Irina V.
Kurtova, Anastasia I.
Pleshkan, Victor V.
Voronezhskaya, Elena E.
Demidyuk, Ilya V.
Kostrov, Sergey V.
Efficiency of Promoters of Human Genes FAP and CTGF at Organism Level in a Danio rerio Model
title Efficiency of Promoters of Human Genes FAP and CTGF at Organism Level in a Danio rerio Model
title_full Efficiency of Promoters of Human Genes FAP and CTGF at Organism Level in a Danio rerio Model
title_fullStr Efficiency of Promoters of Human Genes FAP and CTGF at Organism Level in a Danio rerio Model
title_full_unstemmed Efficiency of Promoters of Human Genes FAP and CTGF at Organism Level in a Danio rerio Model
title_short Efficiency of Promoters of Human Genes FAP and CTGF at Organism Level in a Danio rerio Model
title_sort efficiency of promoters of human genes fap and ctgf at organism level in a danio rerio model
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10138699/
https://www.ncbi.nlm.nih.gov/pubmed/37108352
http://dx.doi.org/10.3390/ijms24087192
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