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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Main Authors: Olga Vladimirovna Orlova, Dina Viktorovna Glazkova, Ramil Rafailovich Mintaev, Galina Mikhailovna Tsyganova, Felix Anatolevich Urusov, German Alexandrovich Shipulin, Elena Vladimirovna Bogoslovskaya
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Language:English
Published: MDPI AG 2023-04-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/11/4/1053
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author Olga Vladimirovna Orlova
Dina Viktorovna Glazkova
Ramil Rafailovich Mintaev
Galina Mikhailovna Tsyganova
Felix Anatolevich Urusov
German Alexandrovich Shipulin
Elena Vladimirovna Bogoslovskaya
author_facet Olga Vladimirovna Orlova
Dina Viktorovna Glazkova
Ramil Rafailovich Mintaev
Galina Mikhailovna Tsyganova
Felix Anatolevich Urusov
German Alexandrovich Shipulin
Elena Vladimirovna Bogoslovskaya
author_sort Olga Vladimirovna Orlova
collection DOAJ
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 doaj.art-ec59fffd0c7041e0bf52d1243d15abce2023-11-17T20:34:20ZengMDPI AGMicroorganisms2076-26072023-04-01114105310.3390/microorganisms11041053Comparative Evaluation of the Activity of Various Lentiviral Vectors Containing Three Anti-HIV GenesOlga Vladimirovna Orlova0Dina Viktorovna Glazkova1Ramil Rafailovich Mintaev2Galina Mikhailovna Tsyganova3Felix Anatolevich Urusov4German Alexandrovich Shipulin5Elena Vladimirovna Bogoslovskaya6Federal State Budgetary Institution “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical Biological Agency, 119121 Moscow, RussiaFederal State Budgetary Institution “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical Biological Agency, 119121 Moscow, RussiaFederal State Budgetary Institution “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical Biological Agency, 119121 Moscow, RussiaFederal State Budgetary Institution “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical Biological Agency, 119121 Moscow, RussiaFederal State Budgetary Institution “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical Biological Agency, 119121 Moscow, RussiaFederal State Budgetary Institution “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical Biological Agency, 119121 Moscow, RussiaFederal State Budgetary Institution “Centre for Strategic Planning and Management of Biomedical Health Risks” of the Federal Medical Biological Agency, 119121 Moscow, RussiaA 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.https://www.mdpi.com/2076-2607/11/4/1053lentiviral vectorsTRIM5ahuman immunodeficiency virus type 1 (HIV-1)C-peptidemiRNA
spellingShingle Olga Vladimirovna Orlova
Dina Viktorovna Glazkova
Ramil Rafailovich Mintaev
Galina Mikhailovna Tsyganova
Felix Anatolevich Urusov
German Alexandrovich Shipulin
Elena Vladimirovna Bogoslovskaya
Comparative Evaluation of the Activity of Various Lentiviral Vectors Containing Three Anti-HIV Genes
Microorganisms
lentiviral vectors
TRIM5a
human immunodeficiency virus type 1 (HIV-1)
C-peptide
miRNA
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 lentiviral vectors
TRIM5a
human immunodeficiency virus type 1 (HIV-1)
C-peptide
miRNA
url https://www.mdpi.com/2076-2607/11/4/1053
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