Gene therapy studies in a canine model of X-linked severe combined immunodeficiency

Hum Gene Ther Clin Dev. 2015 Mar;26(1):50-6. doi: 10.1089/humc.2015.004. Epub 2015 Feb 24.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dogs
  • Genetic Therapy*
  • Humans
  • Retroviridae / genetics*
  • X-Linked Combined Immunodeficiency Diseases / immunology
  • X-Linked Combined Immunodeficiency Diseases / therapy*