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Volume 7
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10.3390/cells7020010
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Article

Optimization of Polycistronic Anti-CCR5 Artificial microRNA Leads to Improved Accuracy of Its Lentiviral Vector Transfer and More Potent Inhibition of HIV-1 in CD4+ T-Cells

by
Felix Urusov
*,
Dina Glazkova
,
Denis Omelchenko
,
Elena Bogoslovskaya
,
Galina Tsyganova
,
Katerina Kersting
,
German Shipulin
and
Vadim Pokrovsky
Department of Molecular Diagnostic and Epidemiology, Federal Budget Institution of Science “Central Research Institute of Epidemiology” of The Federal Service on Customers’ Rights Protection and Human Well-being Surveillance, 111123 Moscow, Russia
*
Author to whom correspondence should be addressed.
Cells 2018, 7(2), 10; https://doi.org/10.3390/cells7020010
Submission received: 15 December 2017 / Revised: 18 January 2018 / Accepted: 2 February 2018 / Published: 4 February 2018
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Abstract

C-C chemokine receptor type 5 (CCR5) is utilized by human immunodeficiency virus (HIV) as a co-receptor for cell entry. Suppression of the CCR5 gene by artificial microRNAs (amiRNAs) could confer cell resistance. In previous work, we created a lentivector that encoded the polycistron of two identical amiRNAs that could effectively suppress CCR5. However, tandem repeats in lentiviral vectors led to deletions of the repeated sequences during reverse transcription of the vector RNA. To solve this problem, we have created a new amiRNA against CCR5, mic1002, which has a different microRNA scaffold and targets a different sequence. Replacing one of the two identical tandem amiRNAs in the polycistron with the mic1002 amiRNA increased the accuracy of its lentiviral vector transfer while retaining its ability to effectively suppress CCR5. A lentiviral vector containing two heterogenic amiRNAs significantly inhibited HIV replication in a vector-transduced human CD4+ lymphocyte culture.
Keywords: HIV gene therapy; CCR5 co-receptor; RNA interference; miRNA; lentiviral vectors HIV gene therapy; CCR5 co-receptor; RNA interference; miRNA; lentiviral vectors

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MDPI and ACS Style

Urusov, F.; Glazkova, D.; Omelchenko, D.; Bogoslovskaya, E.; Tsyganova, G.; Kersting, K.; Shipulin, G.; Pokrovsky, V. Optimization of Polycistronic Anti-CCR5 Artificial microRNA Leads to Improved Accuracy of Its Lentiviral Vector Transfer and More Potent Inhibition of HIV-1 in CD4+ T-Cells. Cells 2018, 7, 10. https://doi.org/10.3390/cells7020010

AMA Style

Urusov F, Glazkova D, Omelchenko D, Bogoslovskaya E, Tsyganova G, Kersting K, Shipulin G, Pokrovsky V. Optimization of Polycistronic Anti-CCR5 Artificial microRNA Leads to Improved Accuracy of Its Lentiviral Vector Transfer and More Potent Inhibition of HIV-1 in CD4+ T-Cells. Cells. 2018; 7(2):10. https://doi.org/10.3390/cells7020010

Chicago/Turabian Style

Urusov, Felix, Dina Glazkova, Denis Omelchenko, Elena Bogoslovskaya, Galina Tsyganova, Katerina Kersting, German Shipulin, and Vadim Pokrovsky. 2018. "Optimization of Polycistronic Anti-CCR5 Artificial microRNA Leads to Improved Accuracy of Its Lentiviral Vector Transfer and More Potent Inhibition of HIV-1 in CD4+ T-Cells" Cells 7, no. 2: 10. https://doi.org/10.3390/cells7020010

APA Style

Urusov, F., Glazkova, D., Omelchenko, D., Bogoslovskaya, E., Tsyganova, G., Kersting, K., Shipulin, G., & Pokrovsky, V. (2018). Optimization of Polycistronic Anti-CCR5 Artificial microRNA Leads to Improved Accuracy of Its Lentiviral Vector Transfer and More Potent Inhibition of HIV-1 in CD4+ T-Cells. Cells, 7(2), 10. https://doi.org/10.3390/cells7020010

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