Liposomal Packaging Generates Wnt Protein with In Vivo Biological Activity

نویسندگان

  • 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
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Antileishmanial Activity of Liposomal Clarithromycin against Leishmania Major Promastigotes

Objective(s)Cutaneous leishmaniasis is a common parasitic disease which is endemic in some parts of the world. In vitro and in vivo studies have shown azithromycin efficacy on some Leishmania species. Because of structural similarity between clarithromycin and azithromycin and efficacy of clarithromycin against intracellular organisms and due to the absence of previous studies in this respect, ...

متن کامل

Beta-catenin Forms Protein Aggregation at High Concentrations in HEK293TCells

Background: The canonical Wnt signal transduction (or the Wnt/β-catenin pathway) plays a crucial role in the development of animals and in carcinogenesis. Beta-catenin is the central component of this signaling pathway. The activation of Wnt/β-catenin signaling results in the cytoplasmic and nuclear accumulation of β-catenin. In the nucleus, β-catenin interacts with the TCF/LEF transcription fa...

متن کامل

Comparison of in vivo Adjuvanticity of Liposomal PO CpG ODN with Liposomal PS CpG ODN: Soluble Leishmania Antigens as a Model

Objective(s)CpG oligodeoxynucleotides (CpG ODNs) have been shown to have potent immunostimulatory adjuvant activity for a wide range of antigens. Due to susceptibility of phosphodiester CpG ODNs (PO CpG) to nuclease degradation, nuclease-resistant phosphorothioate CpG ODNs (PS CpG) were currently utilized in an in vivo model. In this study, according to some recently reported drawbacks with PS ...

متن کامل

Preparation and in vivo evaluation of nanoliposomes containing vancomycin after intravitreal injection in albino rabbits

Objective(s): The in vivo efficacy of nanoliposomal formulation of vancomycin against methicillin-resistant Staphylococcus aureus (MRSA) assessed.Materials and Methods: Nanoliposomal formulations were prepared and characterized. The in vivo study was carried out on rabbits which received liquid culture medium containing MRSA under anesth...

متن کامل

Dev108415 3529..3539

Canonical β-catenin-dependent Wnt signal transduction is important for several biological phenomena, such as cell fate determination, cell proliferation, stem cell maintenance and anterior-posterior axis formation. The hallmark of canonical Wnt signaling is the translocation of β-catenin into the nucleus where it activates gene transcription. However, the mechanisms regulating β-catenin nuclear...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • PLoS ONE

دوره 3  شماره 

صفحات  -

تاریخ انتشار 2008