Authors:
Tushar Menon, Amy L. Firth, Deirdre D. Scripture-Adams, Zoran Galic, Susan J. Qualls, William B. Gilmore, Eugene Ke, Oded Singer, Leif S. Anderson, Alexander R. Bornzin, Ian E. Alexander, Jerome A. Zack, & Inder M. Verma
Summary:
X-linked Severe Combined Immunodeficiency (SCID-X1) is a genetic disease that leaves newborns at high risk of serious infection and a predicted life span of less than 1 year in the absence of a matched bone marrow donor. The disease pathogenesis is due to mutations in the gene encoding the Interleukin-2 receptor gamma chain (IL-2Rγ), leading to a lack of functional lymphocytes. With the leukemogenic concerns of viral gene therapy there is a need to explore alternative therapeutic options. We have utilized induced pluripotent stem cell (iPSC) technology and genome editing mediated by TALENs to generate isogenic subject-specific mutant and gene-corrected iPSC lines. While the subject-derived mutant iPSCs have the capacity to generate hematopoietic precursors and myeloid cells, only wild-type and gene-corrected iPSCs can additionally generate mature NK cells and T cell precursors expressing the correctly spliced IL-2Rγ. This study highlights the potential for the development of autologous cell therapy for SCID-X1 subjects.
Source:
Cell Stem Cell; Vol. 16, Issue 4, 367-372 (04/02/15)