Abstract
Janus kinase-3 (JAK3) deficiency has recently been identified as a cause of severe combined immunodeficiency (SCID) in humans. We used a mouse model of Jak3-deficient SCID to test a gene therapy approach for treatment of this disease. Transfer of a Jak3 retroviral vector to repopulat-ing hematopoietic stem cells resulted in increased numbers of T and B lymphocytes, reversal of hypogammaglobulinemia, restoration of T-cell activation upon stimulation with mitogens, and development of an antigen-specific immune response after immunization. Analysis for vector copy number in lymphoid and myeloid populations showed a large in vivo selective advantage for Jak3-expressing lymphoid cells. These results show that gene replacement is a feasible treatment strategy for this disease and that naturally occurring in vivo selection of corrected cells is an important advantage of this approach.
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Bunting, K., Sangster, M., Ihle, J. et al. Restoration of lymphocyte function in Janus Kinase 3-deficient mice by retroviral-mediated gene transfer. Nat Med 4, 58–64 (1998). https://doi.org/10.1038/nm0198-058
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DOI: https://doi.org/10.1038/nm0198-058
