Foamy virus vector-mediated gene correction of a mouse model of Wiskott-Aldrich syndrome

Toru Uchiyama, Marsilio Adriani, G. Jayashree Jagadeesh, Adam Paine, Fabio Candotti

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    24 Citations (Scopus)

    Abstract

    The Wiskott-Aldrich syndrome (WAS) is an X-linked disorder characterized by eczema, thrombocytopenia and immunodeficiency. Hematopoietic cell transplantation can cure the disease and gene therapy is being tested as an alternative treatment option. In this study, we assessed the use of foamy virus (FV) vectors as a gene transfer system for WAS, using a Was knockout (KO) mouse model. Preliminary experiments using FV vectors expressing the green fluorescent protein under the transcriptional control of the endogenous WAS promoter or a ubiquitously acting chromatin opening element allowed us to define transduction conditions resulting in high (>40%) and long-term in-vivo marking of blood cells after transplantation. In following experiments, Was KO mice were treated with FV vectors containing the human WAS complementary DNA (cDNA). Transplanted animals expressed the WAS protein (WASp) in T and B lymphocytes, as well as platelets and showed restoration of both T-cell receptor-mediated responses and B-cell migration. We also observed recovery of platelet adhesion and podosome formation in dendritic cells (DCs) of treated mice. These data demonstrate that FV vectors can be effective for hematopoietic stem cell (HSC)-directed gene correction of WAS.

    Original languageEnglish
    Pages (from-to)1270-1279
    Number of pages10
    JournalMolecular Therapy
    Volume20
    Issue number6
    DOIs
    Publication statusPublished - 2012 Jun

    ASJC Scopus subject areas

    • Molecular Medicine
    • Molecular Biology
    • Genetics
    • Pharmacology
    • Drug Discovery

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