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Science. 2000 Apr 28;288(5466):627-9.
Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease.
Cavazzana-Calvo M,
Hacein-Bey S,
de Saint Basile G,
Gross F,
Yvon E,
Nusbaum P,
Selz F,
Hue C,
Certain S,
Casanova JL,
Bousso P,
Deist FL,
Fischer A.
INSERM Unit 429, Gene Therapy Laboratory, Cell Therapy Laboratory, Unité d'Immunologie et d'Hématologie Pédiatriques, Hôpital Necker, 75743 Paris Cedex 15, France.
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.
PMID: 10784449 [PubMed - indexed for MEDLINE]