title: Lymphoid regeneration from gene-corrected SCID-X1 subject-derived iPSCs.
abstract: 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.
authors.affiliation: The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Tushar
authors.initials: T
authors.lastname: Menon
authors.affiliation: The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Amy L
authors.initials: AL
authors.lastname: Firth
authors.affiliation: 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.
authors.forename: Deirdre D
authors.initials: DD
authors.lastname: Scripture-Adams
authors.affiliation: 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.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Galic
authors.affiliation: The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Qualls
authors.affiliation: The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Gilmore
authors.affiliation: The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Eugene
authors.initials: E
authors.lastname: Ke
authors.affiliation: The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Oded
authors.initials: O
authors.lastname: Singer
authors.affiliation: The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Leif S
authors.initials: LS
authors.lastname: Anderson
authors.affiliation: The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors.forename: Alexander R
authors.initials: AR
authors.lastname: Bornzin
authors.affiliation: Gene Therapy Research Unit, Children's Medical Research Institute and The Children's Hospital at Westmead, Wentworthville, NSW 2145, Australia.
authors.forename: Ian E
authors.initials: IE
authors.lastname: Alexander
authors.affiliation: 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.
authors.forename: Jerome A
authors.initials: JA
authors.lastname: Zack
authors.affiliation: The Salk Institute of Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, CA 92037, USA. Electronic address: verma@salk.edu.
authors.forename: Inder M
authors.initials: IM
authors.lastname: Verma
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D001426:Bacterial Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D016219:Immunotherapy, Adoptive; D057026:Induced Pluripotent Stem Cells / Q000502:physiology* / Q000637:transplantation; D007223:Infant; D053631:Interleukin Receptor Common gamma Subunit / Q000235:genetics; D007694:Killer Cells, Natural / Q000502:physiology* / Q000637:transplantation; D009154:Mutation / Q000235:genetics; D054504:Precursor Cells, T-Lymphoid / Q000502:physiology* / Q000637:transplantation; D012038:Regeneration; D044968:Regenerative Medicine; D053632:X-Linked Combined Immunodeficiency Diseases / Q000235:genetics / Q000628:therapy*
chemical_list: D015703:Antigens, CD; D001426:Bacterial Proteins; D053631:Interleukin Receptor Common gamma Subunit; D045643:DNA Repair Enzymes