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

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 recep...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2000-04, Vol.288 (5466), p.669-672
Main Authors: Cavazzana-Calvo, Marina, Hacein-Bey, Salima, Geneviève de Saint Basile, Gross, Fabian, Yvon, Eric, Nusbaum, Patrick, Selz, Françoise, Hue, Christophe, Certain, Stéphanie, Casanova, Jean-Laurent, Bousso, Philippe, Le Deist, Françoise, Fischer, Alain
Format: Article
Language:English
Subjects:
AIDS/HIV
Analysis
Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy
Antigens, CD34 - analysis
B lymphocytes
B-Lymphocytes - immunology
Biological and medical sciences
Biotechnology
Blood
Bone marrow, stem cells transplantation. Graft versus host reaction
Care and treatment
CD34 antigen
Cell lines
Cells
Fundamental and applied biological sciences. Psychology
Gene therapy
Gene Transfer Techniques
Genetic Therapy
Genetic Vectors
Health. Pharmaceutical industry
Hematopoietic Stem Cell Transplantation
Hematopoietic Stem Cells - cytology
Humans
Immunoglobulins - blood
Immunologic deficiency syndromes
Immunological deficiency syndromes
Industrial applications and implications. Economical aspects
Infant
Killer Cells, Natural - immunology
Lymphocyte Activation
Lymphocyte Count
Lymphocytes
Medical sciences
Moloney murine leukemia virus - genetics
Mutation
Natural killer cells
Receptors, Antigen, T-Cell - analysis
Receptors, Interleukin - biosynthesis
Receptors, Interleukin - genetics
Severe Combined Immunodeficiency - genetics
Severe Combined Immunodeficiency - therapy
Stem cells
T lymphocytes
T-Lymphocyte Subsets - immunology
T-Lymphocytes - immunology
Transfusions. Complications. Transfusion reactions. Cell and gene therapy
Transgenes
X chromosome
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Summary: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.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.288.5466.669