Liposomal Packaging Generates Wnt Protein with in Vivo Biological Activity

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2008 Aug 14

PMID 18698373

Citations 39

Authors

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

Affiliations

Soon will be listed here.

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.

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