Selection of an optimal promoter for gene transfer in normal B cells

Winiarska,Magdalena; Nowis,Dominika; Firczuk,Malgorzata; Zagozdzon,Agnieszka; Gabrysiak,Magdalena; Sadowski,Radoslaw; Barankiewicz,Joanna; Dwojak,Michal; Golab,Jakub

doi:10.3892/mmr.2017.6974

Selection of an optimal promoter for gene transfer in normal B cells

Authors:
- Magdalena Winiarska
- Dominika Nowis
- Malgorzata Firczuk
- Agnieszka Zagozdzon
- Magdalena Gabrysiak
- Radoslaw Sadowski
- Joanna Barankiewicz
- Michal Dwojak
- Jakub Golab
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Affiliations: Department of Immunology, Center of Biostructure Research, Medical University of Warsaw, 02‑097 Warsaw, Poland, Genomic Medicine, Medical University of Warsaw, 02‑097 Warsaw, Poland
Published online on: July 14, 2017 https://doi.org/10.3892/mmr.2017.6974
Pages: 3041-3048
Copyright: © Winiarska et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gene transfer into normal quiescent human B cells is a challenging procedure. The present study aimed to investigate whether it is possible to increase the levels of transgene expression by using various types of promoters to drive the expression of selected genes‑of‑interest. To produce lentiviral particles, the present study used the 2nd generation psPAX2 packaging vector and the vesicular stomatitis virus ‑expressing envelope vector pMD2.G. Subsequently, lentiviral vectors were generated containing various promoters, including cytomegalovirus (CMV), elongation factor‑1 alpha (EF1α) and spleen focus‑forming virus (SFFV). The present study was unable to induce satisfactory transduction efficiency in quiescent normal B cells; however, infection of normal B cells with Epstein‑Barr virus resulted in increased susceptibility to lentiviral transduction. In addition, the SFFV promoter resulted in a higher level of transgene expression compared with CMV or EF1α promoters. As a proof‑of concept that this approach allows for stable gene expression in normal B cells, the present study used bicistronic lentiviral vectors with genes encoding fluorescent reporter proteins, as well as X‑box binding protein‑1 and binding immunoglobulin protein.

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