Lymphoid regeneration from gene-corrected SCID-X1 subject-derived iPSCs.

Autor:	Menon T; The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Firth AL; The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Scripture-Adams DD; David Geffen School of Medicine at UCLA, University of California, Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-1678; UCLA AIDS Institute, University of California, Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-1678., Galic Z; David Geffen School of Medicine at UCLA, University of California, Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-1678; Broad Stem Cell Research Center, University of California, Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-1678., Qualls SJ; The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Gilmore WB; The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Ke E; The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Singer O; The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Anderson LS; The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Bornzin AR; The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA., Alexander IE; Gene Therapy Research Unit, Children's Medical Research Institute and The Children's Hospital at Westmead, Wentworthville, NSW 2145, Australia., Zack JA; Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-1678; David Geffen School of Medicine at UCLA, University of California, Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-1678; UCLA AIDS Institute, University of California, Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-1678; Broad Stem Cell Research Center, University of California, Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-1678., Verma IM; The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: verma@salk.edu.
Jazyk:	angličtina
Zdroj:	Cell stem cell [Cell Stem Cell] 2015 Apr 02; Vol. 16 (4), pp. 367-72. Date of Electronic Publication: 2015 Mar 12.
DOI:	10.1016/j.stem.2015.02.005
Abstrakt:	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. (Copyright © 2015 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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