Virus-like particles (VLPs) are membrane encapsulated vesicles with multiple uses in medicine and research.  Medical uses include vaccine generation, gene therapy and drug delivery1-3. VLPs are also valuable research tools used for the semi-pure expression, isolation, and study of membrane bound proteins4.  It is this latter use that drew the attention of BPS Bioscience.  We specialize in membrane-bound proteins because they represent a disproportionately high number of FDA-approved therapies and remain an important class of targets for future drug development5

VLP Formation

VLPs have many features that make them attractive research tools.  They lack infectivity and are unable to replicate because they do not contain a viral genome nor any non-structural viral proteins.  Additionally, their uniform size and use of native membrane makes them ideal for use in the isolation of cell-surface molecules. 

VLPs are formed through the self-assembly of viral gag proteins that can be transiently expressed in a variety of cell types (Figure 1)6.  VLPs bud off cells while maintaining membrane proteins in their functional state, preserving native orientation and multimeric state.  Because they are released into the medium, VLPs are easy to purify and concentrate.  Additionally, these particles naturally select lipid-rich regions of membrane that are enriched with membrane proteins7.  This allows for higher yields of co-expressed target proteins beyond what is produced by simple membrane preparations. 

PD-1 PD-L1 VLPCTLA4 B7-1 VLP

BPS can provide custom VLPs expression of disease-relevant or disease modifying membrane targets for assay development or use as reagents.  This new line of products complements and extends studies using highly purified recombinant proteins and studies of cell-based systems.  We have validated the use of this technology by generating functional VLPs and developing subsequent binding assays for the important immuno-oncology checkpoint inhibitors PD-1 and CTLA4 (Figs. 2 and 3). 

CD73 Activity CD39 Activity VLPWe have also developed enzymatic assays using our VLP technology to express the membrane bound enzymes CD39 and CD73, two new promising targets in cancer that regulate ATP hydrolysis to control immune cell function. 

VLP technology can be extended to any membrane-bound or membrane-localized protein.  They are useful for ligand binding or enzymatic analysis of the important class of 7-transmembrane receptors (7TM, or G protein-coupled receptors (GPCRs)).  They are also useful in assays for antibody screening or as a way to stimulate cells in leiu of a co-culture type assay.  Whether you are seeking fully developed research products or help with custom projects, BPS Bioscience can provide the tools and project guidance to help you fulfill your research goals. Contact us today to learn more. 

 

 

References

[1] Doan, L. X., Li, M., Chen, C., and Yao, Q. (2005) Virus-like particles as HIV-1 vaccines, Rev Med Virol 15, 75-88.

[2] Petry, H., Goldmann, C., Ast, O., and Luke, W. (2003) The use of virus-like particles for gene transfer, Curr Opin Mol Ther 5, 524-528.

[3] Galaway, F. A., and Stockley, P. G. (2013) MS2 viruslike particles: a robust, semisynthetic targeted drug delivery platform, Mol Pharm 10, 59-68.

[4] Willis, S., Davidoff, C., Schilling, J., Wanless, A., Doranz, B. J., and Rucker, J. (2008) Virus-like particles as quantitative probes of membrane protein interactions, Biochemistry 47, 6988-6990.

[5] Santos, R., Ursu, O., Gaulton, A., Bento, A. P., Donadi, R. S., Bologa, C. G., Karlsson, A., Al-Lazikani, B., Hersey, A., Oprea, T. I., and Overington, J. P. (2017) A comprehensive map of molecular drug targets, Nat Rev Drug Discov 16, 19-34.

[6] Jalaguier, P., Turcotte, K., Danylo, A., Cantin, R., and Tremblay, M. J. (2011) Efficient production of HIV-1 virus-like particles from a mammalian expression vector requires the N-terminal capsid domain, PLoS One 6, e28314.

[7] Sedy, J. R., Gavrieli, M., Potter, K. G., Hurchla, M. A., Lindsley, R. C., Hildner, K., Scheu, S., Pfeffer, K., Ware, C. F., Murphy, T. L., and Murphy, K. M. (2005) B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator, Nat Immunol 6, 90-98.