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

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Science  28 Apr 2000:
Vol. 288, Issue 5466, pp. 669-672
DOI: 10.1126/science.288.5466.669

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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.

  • * These authors contributed equally to this work.

  • To whom correspondence should be addressed at INSERM Unit 429, Hôpital Necker–Enfants Malades, 149 rue de Sèvres, 75743 Paris Cedex 15, France. E-mail: fischer{at}necker.fr

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