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

Severe combined immunodeficiency-X1 (SCID-X1) is an X-linked inherited diso rder characterized by an early block in T and natural killer (NK) Lymphocyt e differentiation. This block is caused by mutations of the gene encoding t he gamma c cytokine receptor subunit of interleukin-2, -4, -7, -9, and -15 receptors, which participates in the delivery of growth, survival, and diff erentiation signals to early Lymphoid progenitors. After preclinical studie s, a gene therapy trial for SCID-X1 was initiated, based on the use of comp lementary DNA containing a defective gamma c Moloney retrovirus-derived Vec tor and ex vivo infection of CD34(+) cells. After a 10-month follow-up peri od, gamma c transgene-expressing T and NK cells were detected in two patien ts. T, B, and NK cell counts and function, including antigen-specific respo nses, were comparable to those of age-matched controls. Thus, gene therapy was able to provide full correction of disease phenotype and, hence, clinic al benefit.