title: Development of gene therapy: potential in severe combined immunodeficiency due to adenosine deaminase deficiency.
abstract: The history of stem cell gene therapy is strongly linked to the development of gene therapy for severe combined immunodeficiencies (SCID) and especially adenosine deaminase (ADA)-deficient SCID. Here we discuss the developments achieved in over two decades of clinical and laboratory research that led to the establishment of a protocol for the autologous transplant of retroviral vector-mediated gene-modified hematopoietic stem cells, which has proved to be both successful and, to date, safe. Patients in trials in three different countries have shown long-term immunological and metabolic correction. Nevertheless, improvements to the safety profile of viral vectors are underway and will undoubtedly reinforce the position of stem cell gene therapy as a treatment option for ADA-SCID.
authors.affiliation: Centre for immunodeficiency, Molecular immunology Unit, UCL institute of Child Health, London, UK.
authors.forename: Claudia A
authors.initials: CA
authors.lastname: Montiel-Equihua
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Thrasher
authors.forename: H Bobby
authors.initials: HB
authors.lastname: Gaspar
keywords: adenosine deaminase; clinical trial; gene therapy; hematopoietic stem cell; retrovirus; severe combined immunodeficiency