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 kilter (NK) lymphocyte differentiation. This block is caused by mutations of the gene encoding the [Gamma]c cytokine receptor subunit of interteukin-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 [Gamma]c Moloney retrovirus-derived vector and ex vivo infection of [CD34.sup.+] cells. After a 10-month follow-up period, [Gamma]c 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.
In considering diseases that might be ameliorated by gene therapy, a setting in which a selective advantage is conferred by transgene expression, in association with long-lived transduced cells such as [...]