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Drugging a stem cell compartment using Wnt3a protein as a therapeutic.

ABSTRACT: The therapeutic potential of Wnt proteins has long been recognized but challenges associated with in vivo stability and delivery have hindered their development as drug candidates. By exploiting the hydrophobic nature of the protein we provide evidence that exogenous Wnt3a can be delivered in vivo if it is associated with a lipid vesicle. Recombinant Wnt3a associates with the external surface of the lipid membrane; this association stabilizes the protein and leads to prolonged activation of the Wnt pathway in primary cells. We demonstrate the consequences of Wnt pathway activation in vivo using a bone marrow engraftment assay. These data provide validation for the development of WNT3A as a therapeutic protein.

SUBMITTER: Dhamdhere GR

PROVIDER: S-EPMC3882211 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Drugging a stem cell compartment using Wnt3a protein as a therapeutic.

Dhamdhere Girija R GR Fang Mark Y MY Jiang Jie J Lee Katherine K Cheng Du D Olveda Rebecca C RC Liu Bo B Mulligan Kimberley A KA Carlson Jeffery C JC Ransom Ryan C RC Weis William I WI Helms Jill A JA

PloS one 20140106 1

The therapeutic potential of Wnt proteins has long been recognized but challenges associated with in vivo stability and delivery have hindered their development as drug candidates. By exploiting the hydrophobic nature of the protein we provide evidence that exogenous Wnt3a can be delivered in vivo if it is associated with a lipid vesicle. Recombinant Wnt3a associates with the external surface of the lipid membrane; this association stabilizes the protein and leads to prolonged activation of the ...[more]

PMID: 24400074

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