title: Gene therapy of severe combined immunodeficiencies.
abstract: Recent advances in gene transfer in human hematopoietic cells, combined with a better understanding of the genetic aspects of several immunodeficiencies, has offered new opportunities in the domain of gene therapy. Severe combined immunodeficiency (SCID) appear to represent a good model for the application of gene therapy, combining an expected selective advantage for transduced cells, an absence of immunological response to the vector and/or the therapeutic transgene, together with accessibility to hematopoietic stem cells (HSC). Ex vivo retroviral transduction of a therapeutic transgene in HSC prior to transplantation appears to be a particularly effective and long-lasting means of restoring the expression of a mutated gene in the lymphoid lineage. Furthermore, encouraging therapeutic benefits as a result of a gene therapy protocol for the treatment of X-linked severe combined immunodeficiencies (SCID-X1) invites many questions as to the reasons for this therapeutic benefit. This review outlines the results that have been achieved in gene therapy for SCID-X1, ADA-SCID as well as other types of SCID, and discusses the possible relationship between the physiopathology of each disease and the success of relevant trials.
authors: Laboratoire de Thérapie Cellulaire et Génique, Hĵpital Necker Enfants Malades, Paris, France. cavazzan@necker.fr
authors: M
authors: M
authors: Cavazzana-Calvo
authors: S
authors: S
authors: Hacein-Bey
authors: F
authors: F
authors: Yates
authors: J P
authors: JP
authors: de Villartay
authors: F
authors: F
authors: Le Deist
authors: A
authors: A
authors: Fischer
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency; D008040:Genetic Linkage; D015316:Genetic Therapy; D006412:Hematopoietic Stem Cells / Q000378:metabolism; D006801:Humans; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology / Q000628:therapy*; D014960:X Chromosome / Q000235:genetics
chemical_list: D000243:Adenosine Deaminase