title: Development of lentiviral gene therapy for Wiskott Aldrich syndrome.
abstract: BACKGROUND
  Wiskott Aldrich syndrome (WAS) is a rare X-linked primary immunodeficiency. This complex disease is characterised by microthrombocytopenia, recurrent infections, eczema and is associated with a high incidence of autoimmunity and of lymphoid malignancies. WAS is attracting growing attention not only because it highlights the rich cellular and systems biology revolving around cytoskeletal regulation but also because it is candidate for a haematopoietic stem cell gene therapy indication.
  
  
  OBJECTIVE
  As several groups are developing this novel approach, this review discusses the state of the art and challenges in clinical development of gene therapy for WAS, with particular regard to biosafety.
  
  
  METHODS
  In spite of the successes of haematopoietic gene therapy for genetic immune deficiencies, there is a need for more efficient transduction protocols and for vectors with a superior safety profile. Preclinical studies have provided reasonable expectations that haematopoietic gene therapy with a self-inactivated HIV-1-derived vector using the native gene promoter for expression of the WAS transgene will be safe and will lead to the restoration of WAS protein in the haematopoietic and immune system at levels sufficient to provide an improvement in the condition of WAS patients.
  
  
  CONCLUSIONS
  Phase I/II clinical studies will soon be initiated in several European centres to assess the safety and efficacy of this lentiviral vector in WAS patients.
authors.affiliation: Head of Immunology & Gene Therapy Group, INSERM U790, Genethon, 1 bis rue de l'Internationale, 91002 Evry, France. galy@genethon.fr
authors.forename: Anne
authors.initials: A
authors.lastname: Galy
authors.forename: Maria-Grazia
authors.initials: MG
authors.lastname: Roncarolo
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Thrasher
mesh_terms: D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D013601:T-Lymphocytes / Q000276:immunology / Q000637:transplantation; D014161:Transduction, Genetic; D014923:Wiskott-Aldrich Syndrome / Q000628:therapy*; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein