Gene Therapy of Human Severe Combined Immunodeficiency (SCID)-X1 Disease

• Marina Cavazzana-Calvo

  INSERM Unit 429,

• Salima Hacein-Bey

  INSERM Unit 429,

• Geneviève de Saint Basile

  INSERM Unit 429,

• Fabian Gross

  Gene Therapy Laboratory,

• Eric Yvon

  Cell Therapy Laboratory,

• Patrick Nusbaum

  Gene Therapy Laboratory,

• Françoise Selz

  INSERM Unit 429,

• Christophe Hue

  INSERM Unit 429,

• Stéphanie Certain

  INSERM Unit 429,

• Jean-Laurent Casanova

  INSERM Unit 429,

• Philippe Bousso

  INSERM Unit 277, Institut Pasteur, 75730 Paris, France.

• Françoise Le Deist

  INSERM Unit 429,

• Alain Fischer

  INSERM Unit 429,

Abstract

Severe combined immunodeficiency–X1 (SCID-X1) is an X-linked inherited disorder characterized by an early block in T and natural killer (NK) lymphocyte differentiation. This block is caused by mutations of the gene encoding the γc cytokine receptor subunit of interleukin-2, -4, -7, -9, and -15 receptors, which participates in the delivery of growth, survival, and differentiation signals to early lymphoid progenitors. After preclinical studies, a gene therapy trial for SCID-X1 was initiated, based on the use of complementary DNA containing a defective γc Moloney retrovirus–derived vector and ex vivo infection of CD34 + cells. After a 10-month follow-up period, γc transgene–expressing T and NK cells were detected in two patients. T, B, and NK cell counts and function, including antigen-specific responses, were comparable to those of age-matched controls. Thus, gene therapy was able to provide full correction of disease phenotype and, hence, clinical benefit.

Journal

• Science

  Science 288 (5466), 669-672, 2000-04-28

  American Association for the Advancement of Science (AAAS)

Keywords

• Multidisciplinary

Details

• CRID: 1360574095341792256
• NII Article ID: 80011861989
• DOI: 10.1126/science.288.5466.669
• ISSN: 10959203
• ISSN: 00368075
• ISSN: http://id.crossref.org/issn/00368075
• Web Site: https://www.science.org/doi/pdf/10.1126/science.288.5466.669
• Data Source:
  • Crossref
  • CiNii Articles