Gene Therapy of Human Severe Combined Immunodeficiency (SCID)-X1 Disease
Top Cited Papers
- 28 April 2000
- journal article
- clinical trial
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 288 (5466) , 669-672
- https://doi.org/10.1126/science.288.5466.669
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.Keywords
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