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Catch VP22: the hitch-hiker’s ride to gene therapy?

Gene Therapy volume 6, pages 4–5 (1999)Cite this article

One of the major obstacles to the development of any successful gene therapy lies in the delivery of a target protein to sufficient numbers of cells to elicit a therapeutic response. Although viral delivery strategies have proven to be more efficient than non-viral systems, high immunogenicity coupled with the inefficiency of in vivo transduction still limit the extent of gene transfer. The therapeutic benefit achieved by virally targeting a greater proportion of cells may, however, be outweighed by the potentially detrimental effects of the increased host immune response. A novel approach, presented in this month’s issue of ‘Gene Therapy’, which harnesses the unique ability of the herpes simplex type 1 (HSV-1) VP22 protein to spread from cell to cell, may provide a means to overcome this paradox.1

The HSV-1 VP22 protein forms part of the viral tegument, a poorly understood region of the virion located between the capsid and the envelope.2 The recent discovery that VP22 possesses novel trafficking properties in both transfected and virally infected cells3 has aroused significant interest in its potential as a protein delivery vehicle. In infected cells, cytoplasmically located VP22 is rapidly excreted via a Golgi-independent pathway and is subsequently imported into neighbouring uninfected cells by a process requiring an intact actin cytoskeleton. Imported VP22 accumulates in the nucleus, where it may affect the regulation of cellular factors, increasing susceptibility to HSV infection3. The inter-cellular spread of VP22 appears to be a highly efficient process, with VP22 synthesised in one microinjected cell capable of reaching up to 200 surrounding cells.3

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References

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Authors
  1. Anthea L Murphy
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  2. Stephen J Murphy
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Murphy, A., Murphy, S. Catch VP22: the hitch-hiker’s ride to gene therapy?. Gene Ther 6, 4–5 (1999). https://doi.org/10.1038/sj.gt.3300849

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