Nathan T. Morrell, Philipp Leucht, Ludan Zhao, Jae-Beom Kim, Derk ten Berge, Karthik Ponnusamy, A. Lyonel Carre, Henryk Dudek, Marie Zachlederova, Michael McElhaney, Shirley Brunton, Janet Gunzner, Marinella Callow, Paul Polakis, Mike Costa, Xiaoyan M. Zhang, Jill A. Helms, Roel Nusse

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.