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Cells 2018, 7(2), 10; https://doi.org/10.3390/cells7020010

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

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
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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. View Full-Text
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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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.

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