Gene therapy for Wiskott-Aldrich Syndrome

Curr Gene Ther. 2014;14(6):413-21. doi: 10.2174/1566523214666140918103731.


The Wiskott-Aldrich Syndrome (WAS) is a monogenic X-linked primary immunodeficiency characterised also by thrombocytopenia, eczema, and a high susceptibility to develop tumours and autoimmunity. WAS patients have a severely reduced life expectancy, unless they undergo a successful HLA-matched haematopoietic stem cell (HSC) transplantation. However, several WAS patients lack a compatible donor and complications, such as autoimmunity, can arise in a significant fraction of HSC transplanted patients. Administration of WAS gene-corrected autologous HSC represents an alternative therapeutic approach, potentially applicable to all WAS patients. To this aim, several gene therapy approaches for WAS using initially γ-retroviral vectors (RVs) and subsequently HIV-based lentiviral vectors (LVs) have been developed. In the present review, we will first describe the results of the preclinical studies conducted in the murine model of WAS and then discuss the outcome of different phase I/II clinical trials using RV or LV- transduced HSC. Both gene therapy approaches led to restored WASP expression, correction of functional defects and clinical improvement. While RV-mediated gene therapy was associated with a high occurrence of leukaemia, results obtained in the first patients treated with LV-based HSC gene therapy indicate a safer risk-benefit profile.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Genetic Therapy*
  • Genetic Vectors / therapeutic use*
  • Humans
  • Mice
  • Wiskott-Aldrich Syndrome / genetics*
  • Wiskott-Aldrich Syndrome / therapy*
  • Wiskott-Aldrich Syndrome Protein Family / genetics*


  • Wiskott-Aldrich Syndrome Protein Family