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Volume 15
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10.3390/cells15181704
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Article

Bicistronic Lentiviral Architecture Increases Surface Density of Membrane-Associated HIV Entry Inhibitors and Confers Tropism-Independent Protection to Modified Cells

by
Yaroslava V. Chervyakova
1,
Alena V. Smirnova
1,
Andrei Siniavin
2,
Vasilisa E. Soldatova
1,
Diana D. Gamzik
3,
Anna V. Tvorogova
1,
Islam M. Nakastoev
4,
Alexander V. Filatov
5,
Natalia A. Kruglova
1 and
Alexandra Konstantia Y. Maslennikova
1,*
1
Institute of Gene Biology, Russian Academy of Sciences, Ministry of Science and Higher Education of the Russian Federation, Moscow 119334, Russia
2
Federal State Budget Institution “National Research Centre for Epidemiology and Microbiology Named After Honorary Academician N. F. Gamaleya”, The Ministry of Health of the Russian Federation, Moscow 123089, Russia
3
Zoological Institute of the Russian Academy of Sciences, Saint Petersburg 199034, Russia
4
Federal State Budgetary Institution National Medical Research Centre for Hematology, The Ministry of Health of the Russian Federation, Moscow 125167, Russia
5
National Research Center Institute of Immunology, Federal Medical Biological Agency of Russia, Moscow 115522, Russia
*
Author to whom correspondence should be addressed.
Cells 2026, 15(18), 1704; https://doi.org/10.3390/cells15181704 (registering DOI)
Submission received: 18 August 2026 / Revised: 15 September 2026 / Accepted: 16 September 2026 / Published: 19 September 2026
(This article belongs to the Section Cell and Gene Therapy)
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Abstract

Background: Previous studies have demonstrated the efficacy of membrane-anchored C-peptides against HIV and have shown that the surface expression level of these peptides is critical for effective protective activity. Methods: Bicistronic genetic constructs were designed for GPI-anchored expression of protective C-peptides on the cell membrane. The constructs were delivered using lentiviral vectors and tested in primary CD4+ lymphocytes and hematopoietic stem cells. Results: The bicistronic configuration significantly enhanced surface expression levels compared to monocistronic constructs and allowed simultaneous expression of two distinct protective peptides, thereby potentiating their activity. Lentiviral vectors harboring these constructs conferred robust protection to primary CD4+ lymphocytes against HIV infection irrespective of viral tropism and provided a selective advantage to transduced cells upon challenge with replication-competent HIV strains. The bicistronic construct was also suitable for lentiviral transduction of hematopoietic stem cells. Conclusions: These findings establish bicistronic GPI-anchored C-peptide expression as a promising platform for generating HIV-resistant immune cells and highlight its potential for ex vivo gene therapy.
Keywords: gene therapy; HIV fusion inhibitor; CD4+ T lymphocytes; hematopoietic stem cells; ex vivo cell engineering; lentiviral delivery; GPI-anchored C-peptides; HIV resistance; inducible expression system gene therapy; HIV fusion inhibitor; CD4+ T lymphocytes; hematopoietic stem cells; ex vivo cell engineering; lentiviral delivery; GPI-anchored C-peptides; HIV resistance; inducible expression system

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MDPI and ACS Style

Chervyakova, Y.V.; Smirnova, A.V.; Siniavin, A.; Soldatova, V.E.; Gamzik, D.D.; Tvorogova, A.V.; Nakastoev, I.M.; Filatov, A.V.; Kruglova, N.A.; Maslennikova, A.K.Y. Bicistronic Lentiviral Architecture Increases Surface Density of Membrane-Associated HIV Entry Inhibitors and Confers Tropism-Independent Protection to Modified Cells. Cells 2026, 15, 1704. https://doi.org/10.3390/cells15181704

AMA Style

Chervyakova YV, Smirnova AV, Siniavin A, Soldatova VE, Gamzik DD, Tvorogova AV, Nakastoev IM, Filatov AV, Kruglova NA, Maslennikova AKY. Bicistronic Lentiviral Architecture Increases Surface Density of Membrane-Associated HIV Entry Inhibitors and Confers Tropism-Independent Protection to Modified Cells. Cells. 2026; 15(18):1704. https://doi.org/10.3390/cells15181704

Chicago/Turabian Style

Chervyakova, Yaroslava V., Alena V. Smirnova, Andrei Siniavin, Vasilisa E. Soldatova, Diana D. Gamzik, Anna V. Tvorogova, Islam M. Nakastoev, Alexander V. Filatov, Natalia A. Kruglova, and Alexandra Konstantia Y. Maslennikova. 2026. "Bicistronic Lentiviral Architecture Increases Surface Density of Membrane-Associated HIV Entry Inhibitors and Confers Tropism-Independent Protection to Modified Cells" Cells 15, no. 18: 1704. https://doi.org/10.3390/cells15181704

APA Style

Chervyakova, Y. V., Smirnova, A. V., Siniavin, A., Soldatova, V. E., Gamzik, D. D., Tvorogova, A. V., Nakastoev, I. M., Filatov, A. V., Kruglova, N. A., & Maslennikova, A. K. Y. (2026). Bicistronic Lentiviral Architecture Increases Surface Density of Membrane-Associated HIV Entry Inhibitors and Confers Tropism-Independent Protection to Modified Cells. Cells, 15(18), 1704. https://doi.org/10.3390/cells15181704

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