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Selective transduction of protease-rich tumors by matrix-metalloproteinase-targeted retroviral vectors

Gene Therapy volume 6, pages 1552–1557 (1999)Cite this article

Abstract

We recently showed that retroviral vectors can be targeted through protease substrate interactions. Infectivity is blocked by a polypeptide fused to the viral envelope glycoprotein (SU) and is restored when a protease cleaves the connecting linker, releasing the inhibitory polypeptide from the viral surface. Protease specificity is achieved by engineering the sequence of the linker. Here, using two different matrix-metalloproteinase (MMP)-activatable vectors, we demonstrated highly efficient and selective transduction of MMP-rich target cells in a heterogeneous cell population. In vivo, the MMP-targeted vectors showed strong selectivity for MMP-rich tumor xenografts. Protease-activatable vectors offer new possibilities for in vivo targeting of gene delivery.

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Acknowledgements

We thank Drs K Siemering and G Murphy, respectively, for their kind gifts of the GFP expression plasmid, mGFPS65T and the MT1-MMP expressing HT1080 cell line. This work was supported by the UK Medical Research Council Center (KWP and SJR), Mayo and Siebens Foundations (KWP, RGV and SJR), Singapore Nanyang Technological University/National Institute of Education (KWP), Centre National de la Recherche Scientifique (FLC) and Imperial Cancer Research Fund (RGV).

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Authors and Affiliations

  1. Molecular Medicine Program, Guggenheim 18, Mayo Foundation, Rochester, MN, USA

    K-W Peng, R G Vile & S J Russell

  2. Vectorologie Rétrovirale et Thérapie Génique, INSERM U412 – Unité de Virologie Humaine, Ecole Normale Supérieure de Lyon, Lyon, France

    F-L Cosset

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  1. K-W Peng
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  2. R G Vile
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Peng, KW., Vile, R., Cosset, FL. et al. Selective transduction of protease-rich tumors by matrix-metalloproteinase-targeted retroviral vectors. Gene Ther 6, 1552–1557 (1999). https://doi.org/10.1038/sj.gt.3300982

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