X-linked severe combined immunodeficiency: from molecular cause to gene therapy within seven years

Abstract

X-linked severe combined immunodeficiency (XSCID) is the most common form of SCID. The discovery of the genetic defect in this disease, namely mutations in the gene encoding the common cytokine receptor γ chain, γ_c, was reported just over seven years ago. In the subsequent period, a tremendous amount of knowledge about the biology and function of this protein has been generated. Moreover, γ_c-knockout mice have been generated and their immune systems successfully reconstituted by gene therapy. Furthermore, initial attempts at using gene therapy to treat patients with XSCID have been successful for more than ten months, making this disease perhaps the most promising to date for treatment with such a strategy.