title: Gene therapy studies in a canine model of X-linked severe combined immunodeficiency.
abstract: Since the occurrence of T cell leukemias in the original human γ-retroviral gene therapy trials for X-linked severe combined immunodeficiency (XSCID), considerable effort has been devoted to developing safer vectors. This review summarizes gene therapy studies performed in a canine model of XSCID to evaluate the efficacy of γ-retroviral, lentiviral, and foamy viral vectors for treating XSCID and a novel method of vector delivery. These studies demonstrate that durable T cell reconstitution and thymopoiesis with no evidence of any serious adverse events and, in contrast to the human XSCID patients, sustained marking in myeloid cells and B cells with reconstitution of normal humoral immune function can be achieved for up to 5 years without any pretreatment conditioning. The presence of sustained levels of gene-marked T cells, B cells, and more importantly myeloid cells for almost 5 years is highly suggestive of transduction of either multipotent hematopoietic stem cells or very primitive committed progenitors.
authors.affiliation: 1 Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania , Philadelphia, PA 19104.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Felsburg
authors.forename: Suk See
authors.initials: SS
authors.lastname: De Ravin
authors.forename: Harry L
authors.initials: HL
authors.lastname: Malech
authors.forename: Brian P
authors.initials: BP
authors.lastname: Sorrentino
authors.forename: Christopher
authors.initials: C
authors.lastname: Burtner
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Kiem
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004285:Dogs; D015316:Genetic Therapy; D006801:Humans; D012190:Retroviridae / Q000235:genetics*; D053632:X-Linked Combined Immunodeficiency Diseases / Q000276:immunology / Q000628:therapy*