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Comparative Evaluation of the Activity of Various Lentiviral Vectors Containing Three Anti-HIV Genes

A promising direction in the treatment of HIV infection is a gene therapy approach based on the insertion of antiviral genes aimed at inhibiting HIV replication into the genome of host cells. We obtained six constructs of lentiviral vectors with different arrangements of three antiviral genes: micro...

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Autores principales: Orlova, Olga Vladimirovna, Glazkova, Dina Viktorovna, Mintaev, Ramil Rafailovich, Tsyganova, Galina Mikhailovna, Urusov, Felix Anatolevich, Shipulin, German Alexandrovich, Bogoslovskaya, Elena Vladimirovna
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141122/
https://www.ncbi.nlm.nih.gov/pubmed/37110476
http://dx.doi.org/10.3390/microorganisms11041053
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author Orlova, Olga Vladimirovna
Glazkova, Dina Viktorovna
Mintaev, Ramil Rafailovich
Tsyganova, Galina Mikhailovna
Urusov, Felix Anatolevich
Shipulin, German Alexandrovich
Bogoslovskaya, Elena Vladimirovna
author_facet Orlova, Olga Vladimirovna
Glazkova, Dina Viktorovna
Mintaev, Ramil Rafailovich
Tsyganova, Galina Mikhailovna
Urusov, Felix Anatolevich
Shipulin, German Alexandrovich
Bogoslovskaya, Elena Vladimirovna
author_sort Orlova, Olga Vladimirovna
collection PubMed
description A promising direction in the treatment of HIV infection is a gene therapy approach based on the insertion of antiviral genes aimed at inhibiting HIV replication into the genome of host cells. We obtained six constructs of lentiviral vectors with different arrangements of three antiviral genes: microRNAs against the CCR5 gene, the gene encoding the C-peptide, and the gene encoding the modified human TRIM5a protein. We found that despite containing the same genes, these vectors were produced at different titers and had different effects on cell viability, transduction efficiency, and expression stability. Comparative evaluation of the antiviral activity of three of the six developed vectors that showed stable expression was carried out using the continuous SupT1 lymphocytic cell line. All of the vectors protected cells from HIV infection: the viral load was several orders of magnitude lower than in control cells, and with one vector, complete cessation of virus growth in modified cells was achieved.
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spelling pubmed-101411222023-04-29 Comparative Evaluation of the Activity of Various Lentiviral Vectors Containing Three Anti-HIV Genes Orlova, Olga Vladimirovna Glazkova, Dina Viktorovna Mintaev, Ramil Rafailovich Tsyganova, Galina Mikhailovna Urusov, Felix Anatolevich Shipulin, German Alexandrovich Bogoslovskaya, Elena Vladimirovna Microorganisms Article A promising direction in the treatment of HIV infection is a gene therapy approach based on the insertion of antiviral genes aimed at inhibiting HIV replication into the genome of host cells. We obtained six constructs of lentiviral vectors with different arrangements of three antiviral genes: microRNAs against the CCR5 gene, the gene encoding the C-peptide, and the gene encoding the modified human TRIM5a protein. We found that despite containing the same genes, these vectors were produced at different titers and had different effects on cell viability, transduction efficiency, and expression stability. Comparative evaluation of the antiviral activity of three of the six developed vectors that showed stable expression was carried out using the continuous SupT1 lymphocytic cell line. All of the vectors protected cells from HIV infection: the viral load was several orders of magnitude lower than in control cells, and with one vector, complete cessation of virus growth in modified cells was achieved. MDPI 2023-04-18 /pmc/articles/PMC10141122/ /pubmed/37110476 http://dx.doi.org/10.3390/microorganisms11041053 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
Orlova, Olga Vladimirovna
Glazkova, Dina Viktorovna
Mintaev, Ramil Rafailovich
Tsyganova, Galina Mikhailovna
Urusov, Felix Anatolevich
Shipulin, German Alexandrovich
Bogoslovskaya, Elena Vladimirovna
Comparative Evaluation of the Activity of Various Lentiviral Vectors Containing Three Anti-HIV Genes
title Comparative Evaluation of the Activity of Various Lentiviral Vectors Containing Three Anti-HIV Genes
title_full Comparative Evaluation of the Activity of Various Lentiviral Vectors Containing Three Anti-HIV Genes
title_fullStr Comparative Evaluation of the Activity of Various Lentiviral Vectors Containing Three Anti-HIV Genes
title_full_unstemmed Comparative Evaluation of the Activity of Various Lentiviral Vectors Containing Three Anti-HIV Genes
title_short Comparative Evaluation of the Activity of Various Lentiviral Vectors Containing Three Anti-HIV Genes
title_sort comparative evaluation of the activity of various lentiviral vectors containing three anti-hiv genes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141122/
https://www.ncbi.nlm.nih.gov/pubmed/37110476
http://dx.doi.org/10.3390/microorganisms11041053
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