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Engineered retroviral virus-like particles for receptor targeting

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Abstract

Retroviral gag proteins, as well as fragments minimally containing the capsid (CA) and nucleocapsid (NC) subunits of Gag, are able to spontaneously assemble into virus-like particles (VLPs). This occurs in mammalian and bacterial cells as well as in in vitro systems. In every circumstance, nucleic acids are incorporated into the forming particles. Here, we took advantage of an in vitro system for the generation of non-enveloped Mason-Pfizer monkey virus (M-PMV) VLPs derived from a self-assembling CA-NC subunit of Gag. These VLPs were modified through N-terminal extension of CA-NC with short oligopeptides that, after the assembly process, were exposed on the surface of VLPs. The employed N-terminal modifications allowed specific interaction with target cells expressing prostate-specific membrane antigen. Using this system, we were able to incorporate selected siRNA into forming VLPs and deliver it into the cytosol of target cells. In comparison with other viral vectors designed for targeted transgene delivery, this M-PMV VLP system represents the lowest risk of generating virus-associated pathology, as the VLPs do not contain any viral coding sequences and are formed in a cell-free system.

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Acknowledgments

We would like to thank Michaela Rumlova for kindly providing expression plasmids and polyclonal anti-capsid protein antibody, and Jan Konvalinka for kindly providing stably transfected HEK 293T cells. This research was supported financially by Czech Science Foundation grant P302/12/1895 and Czech Ministry of Education grant LH12011.

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The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Biochemistry and Microbiology, Institute of Chemical Technology Prague, Technicka 5, 166 28, Prague 6, Czech Republic

    Irena Voráčková, Pavel Ulbrich & Tomáš Ruml

  2. Biology Department, Boston College, 140 Commonwealth Avenue, Chestnut Hill, MA, USA

    William E. Diehl

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  1. Irena Voráčková
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  2. Pavel Ulbrich
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  3. William E. Diehl
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  4. Tomáš Ruml
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Correspondence to Pavel Ulbrich or Tomáš Ruml.

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Voráčková, I., Ulbrich, P., Diehl, W.E. et al. Engineered retroviral virus-like particles for receptor targeting. Arch Virol 159, 677–688 (2014). https://doi.org/10.1007/s00705-013-1873-6

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