Liposomal packaging generates Wnt protein with in vivo biological activity

PLoS One. 2008 Aug 13;3(8):e2930. doi: 10.1371/journal.pone.0002930.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Cell Culture Techniques
  • Liposomes
  • Male
  • Membrane Lipids / physiology
  • Mice
  • Mice, Inbred Strains
  • Signal Transduction
  • Wnt Proteins / antagonists & inhibitors
  • Wnt Proteins / biosynthesis*
  • Wnt Proteins / isolation & purification
  • Wnt Proteins / physiology*
  • Wnt3 Protein
  • Wnt3A Protein

Substances

  • Liposomes
  • Membrane Lipids
  • Wnt Proteins
  • Wnt3 Protein
  • Wnt3A Protein
  • Wnt3a protein, mouse