Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease |
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Authors: | Cavazzana-Calvo M Hacein-Bey S de Saint Basile G Gross F Yvon E Nusbaum P Selz F Hue C Certain S Casanova J L Bousso P Deist F L Fischer A |
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Affiliation: | INSERM Unit 429, Gene Therapy Laboratory, Cell Therapy Laboratory, Unité d'Immunologie et d'Hématologie Pédiatriques, H?pital Necker, 75743 Paris Cedex 15, France. |
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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 gammac 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 gammac Moloney retrovirus-derived vector and ex vivo infection of CD34+ cells. After a 10-month follow-up period, gammac 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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