Sustained Correction of X-Linked Severe Combined Immunodeficiency by ex Vivo Gene Therapy

Gene therapy was used in five boys with X-linked severe combined immunodeficiency disease. In this disorder, a mutation disables the common γ (γc) chain, a component of five cytokine receptors that are essential for the development of T cells and natural killer cells. The disease is fatal within the first year of life unless treated with bone marrow transplantation. The immune system was restored in four patients, who remain well and have required no further treatment during follow-up of up to two years. Gene therapy was used in five boys with X-linked immunodeficiency disease. Deficiency of the common γ (γc) chain, an X-linked disorder, causes the most frequent form of severe combined immunodeficiency disease. 1 , 2 The γc chain is an essential component of five cytokine receptors, all of which are necessary for the development of T cells and natural killer cells. Without the γc chain, there is a complete absence of mature T and natural killer cells, whereas B cells are usually present in normal or increased numbers. Severe combined immunodeficiency is fatal during the first year of life because of severe, recurrent infections, unless transplantation of hematopoietic stem cells restores T-cell function. 3 , . . .