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

X-linked severe combined immunodeficiency due to a mutation in the gene encoding the common gamma (gamma(c)) chain is a lethal condition that can be cured by allogeneic stem-cell transplantation. We investigated whether infusion of autologous hematopoietic stem cells that had been transduced in vitro with the gamma(c) gene can restore the immune system in patients with severe combined immunodeficiency.

CD34+ bone marrow cells from five boys with X-linked severe combined immunodeficiency were transduced ex vivo with the use of a defective retroviral vector. Integration and expression of the gamma(c) transgene and development of lymphocyte subgroups and their functions were sequentially analyzed over a period of up to 2.5 years after gene transfer.