Lymphoid Regeneration From Gene-Corrected SCID-X1 Subject-Derived iPSCs

Cell Stem Cell. 2015 Apr 2;16(4):367-72. doi: 10.1016/j.stem.2015.02.005. Epub 2015 Mar 12.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, CD / metabolism
  • Bacterial Proteins / metabolism
  • Cell Differentiation / genetics
  • Cell Line
  • DNA Repair
  • DNA Repair Enzymes / metabolism
  • Genetic Therapy / methods*
  • Humans
  • Immunotherapy, Adoptive*
  • Induced Pluripotent Stem Cells / physiology*
  • Induced Pluripotent Stem Cells / transplantation
  • Infant
  • Interleukin Receptor Common gamma Subunit / genetics
  • Killer Cells, Natural / physiology*
  • Killer Cells, Natural / transplantation
  • Mutation / genetics
  • Precursor Cells, T-Lymphoid / physiology*
  • Precursor Cells, T-Lymphoid / transplantation
  • Regeneration*
  • Regenerative Medicine*
  • X-Linked Combined Immunodeficiency Diseases / genetics
  • X-Linked Combined Immunodeficiency Diseases / therapy*


  • Antigens, CD
  • Bacterial Proteins
  • Interleukin Receptor Common gamma Subunit
  • DNA Repair Enzymes