Liposomal packaging generates Wnt protein with in vivo biological activity.
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.
Morrell
Nathan T
NT
Division of Plastic and Reconstructive Surgery, Department of Surgery, Stanford University, Stanford, California, United States of America.
Leucht
Philipp
P
Zhao
Ludan
L
Kim
Jae-Beom
JB
ten Berge
Derk
D
Ponnusamy
Karthik
K
Carre
A Lyonel
AL
Dudek
Henryk
H
Zachlederova
Marie
M
McElhaney
Michael
M
Brunton
Shirley
S
Gunzner
Janet
J
Callow
Marinella
M
Polakis
Paul
P
Costa
Mike
M
Zhang
Xiaoyan M
XM
Helms
Jill A
JA
Nusse
Roel
R
D000818:Animals; D018929:Cell Culture Techniques; D008081:Liposomes; D008297:Male; D008563:Membrane Lipids / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D015398:Signal Transduction; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000302:isolation & purification / Q000502:physiology*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
D008081:Liposomes; D008563:Membrane Lipids; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; C555511:Wnt3a protein, mouse