Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease

M Cavazzana-Calvo, S Hacein-Bey, GS Basile, F Gross… - Science, 2000 - science.org
M Cavazzana-Calvo, S Hacein-Bey, GS Basile, F Gross, E Yvon, P Nusbaum, F Selz, C Hue
Science, 2000science.org
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 …
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.
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