Vol 56(2022) N 1 p. 107-114; DOI 10.1134/S0026893322010083
F.A. Urusov1,2*, D.V. Glazkova1, G.M. Tsyganova1, D.V. Pozdyshev3, E.V. Bogoslovskaya1, G.A. Shipulin1
The Titer of the Lentiviral Vector Encoding Chimeric TRIM5α-HRH Gene is Reduced Due to Expression of TRIM5α-HRH in Producer Cells and the Negative Effect of Efla Promoter1Center for Strategic Planning and Management of Medical and Biological Health Risks, Federal Medical-Biological Agency of the Russian Federation, Moscow, 119992 Russia
2Izmerov Research Institute of Occupational Health, Moscow, 105275 Russia
3Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, 119992 Russia
Received - 2021-04-02; Revised - 2021-06-11; Accepted - 2021-06-11
The chimeric protein TRIM5α-HRH is a promising antiviral factor for HIV-1 gene therapy. This protein is able to protect cells from HIV-1 by blocking the virus in the cytoplasm. We are developing protocol of HIV-1 gene therapy, which involves the delivery of the TRIM5α-HRH gene into CD4+ T-lymphocytes by lentiviral vectors (LVs). However, LVs containing TRIM5α-HRH have a low infectious titer, which prevents effective T cell modification. Here, we found that the expression of TRIM5α-HRH during pseudoviral particle production in HEK293 T cells, as well as the presence of the Eflα promoter in our construction are responsible for titer reduction. These results allow us to determine the directions for further optimization of LV with the TRIM5α-HRH gene to improve its infectious titer.
TRIM5α, TRIM5α-HRH, gene therapy, HIV-1, Eflα, lentiviral vector