Research ArticleGene Therapy

Lentiviral hematopoietic stem cell gene therapy for X-linked severe combined immunodeficiency

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Science Translational Medicine  20 Apr 2016:
Vol. 8, Issue 335, pp. 335ra57
DOI: 10.1126/scitranslmed.aad8856

SCID gene therapy comes of age

Diseases caused by mutations in single genes are prime candidates for gene therapy. X-linked severe combined immunodeficiency (SCID-X1) patients have mutations in IL2RG, which encodes the common γ chain of several interleukin receptors, resulting in lack of adaptive immune cells. Gene therapy has shown promise in SCID infants but failed in older SCID-X1 children. Now, De Ravin et al. report that lentiviral gene therapy with nonmyeloablative conditioning corrected multiple immune cell types in five older SCID-X1 patients whose symptoms persisted despite undergoing hematopoietic stem cell transplant(s) as infants. Humoral immunity restoration with normal immunoglobulin production and responses to immunization is confirmed in the first two patients with longer follow-up.