Lentiviral-mediated gene therapy leads to improvement of B-cell functionality in a murine model of Wiskott-Aldrich syndrome

Marita Bosticardo, Elena Draghici, Francesca Schena, Aisha Vanessa Sauer, Elena Fontana, Maria Carmina Castiello, Marco Catucci, Michela Locci, Luigi Naldini, Alessandro Aiuti, Maria Grazia Roncarolo, Pietro Luigi Poliani, Elisabetta Traggiai, Anna Villa

Research output: Contribution to journalArticlepeer-review


Background: Wiskott-Aldrich syndrome (WAS) is an X-linked primary immunodeficiency characterized by thrombocytopenia, eczema, infections, autoimmunity, and lymphomas. Transplantation of hematopoietic stem cells from HLA-identical donors is curative, but it is not available to all patients. We have developed a gene therapy (GT) approach for WAS by using a lentiviral vector encoding for human WAS promoter/cDNA (w1.6W) and demonstrated its preclinical efficacy and safety. Objective: To evaluate B-cell reconstitution and correction of B-cell phenotype in GT-treated mice. Methods: We transplanted Was -/- mice sublethally irradiated (700 rads) with lineage marker-depleted bone marrow wild-type cells, Was-/- cells untransduced or transduced with the w1.6W lentiviral vector and analyzed B-cell reconstitution in bone marrow, spleen, and peritoneum. Results: Here we show that WAS protein+ B cells were present in central and peripheral B-cell compartments from GT-treated mice and displayed the strongest selective advantage in the splenic marginal zone and peritoneal B1 cell subsets. After GT, splenic architecture was improved and B-cell functions were restored, as demonstrated by the improved antibody response to pneumococcal antigens and the reduction of serum IgG autoantibodies. Conclusion: WAS GT leads to improvement of B-cell functions, even in the presence of a mixed chimerism, further validating the clinical application of the w1.6W lentiviral vector.

Original languageEnglish
JournalJournal of Allergy and Clinical Immunology
Issue number6
Publication statusPublished - Jun 2011


  • autoimmunity
  • B cells
  • Gene therapy
  • lentiviral vectors
  • primary immunodeficiency
  • Wiskott-Aldrich syndrome

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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