Cancer Institute A national cancer institute
designated cancer center

Roeland Nusse

Publication Details

  • Liposomal Packaging Generates Wnt Protein with In Vivo Biological Activity PLOS ONE Morrell, N. T., Leucht, P., Zhao, L., Kim, J., Ten Berge, D., Ponnusamy, K., Carre, A. L., Dudek, H., Zachlederova, M., McElhaney, M., Brunton, S., Gunzner, J., Callow, M., Polakis, P., Costa, M., Zhang, X. M., Helms, J. A., Nusse, R. 2008; 3 (8)

    Abstract:

    Wnt signals exercise strong cell-biological and regenerative effects of considerable therapeutic value. There are, however, no specific Wnt agonists and no method for in vivo delivery of purified Wnt proteins. Wnts contain lipid adducts that are required for activity and we exploited this lipophilicity by packaging purified Wnt3a protein into lipid vesicles. Rather than being encapsulated, Wnts are tethered to the liposomal surface, where they enhance and sustain Wnt signaling in vitro. Molecules that effectively antagonize soluble Wnt3a protein but are ineffective against the Wnt3a signal presented by a cell in a paracrine or autocrine manner are also unable to block liposomal Wnt3a activity, suggesting that liposomal packaging mimics the biological state of active Wnts. When delivered subcutaneously, Wnt3a liposomes induce hair follicle neogenesis, demonstrating their robust biological activity in a regenerative context.

    View details for DOI 10.1371/journal.pone.0002930

    View details for Web of Science ID 000264412600016

    View details for PubMedID 18698373

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