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Targeted gene addition in human CD34(+) hematopoietic cells for correction of X-linked chronic granulomatous disease.
De Ravin, Suk See; Reik, Andreas; Liu, Pei-Qi; Li, Linhong; Wu, Xiaolin; Su, Ling; Raley, Castle; Theobald, Narda; Choi, Uimook; Song, Alexander H; Chan, Andy; Pearl, Jocelynn R; Paschon, David E; Lee, Janet; Newcombe, Hannah; Koontz, Sherry; Sweeney, Colin; Shivak, David A; Zarember, Kol A; Peshwa, Madhusudan V; Gregory, Philip D; Urnov, Fyodor D; Malech, Harry L.
Afiliación
  • De Ravin SS; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Reik A; Sangamo BioSciences, Inc., Richmond, California, USA.
  • Liu PQ; Sangamo BioSciences, Inc., Richmond, California, USA.
  • Li L; MaxCyte, Inc., Gaithersburg, Maryland, USA.
  • Wu X; Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, Maryland, USA.
  • Su L; Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, Maryland, USA.
  • Raley C; Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, Maryland, USA.
  • Theobald N; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Choi U; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Song AH; Sangamo BioSciences, Inc., Richmond, California, USA.
  • Chan A; Sangamo BioSciences, Inc., Richmond, California, USA.
  • Pearl JR; Sangamo BioSciences, Inc., Richmond, California, USA.
  • Paschon DE; Sangamo BioSciences, Inc., Richmond, California, USA.
  • Lee J; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Newcombe H; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Koontz S; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Sweeney C; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Shivak DA; Sangamo BioSciences, Inc., Richmond, California, USA.
  • Zarember KA; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
  • Peshwa MV; Cancer Research Technology Program, Leidos Biomedical Research, Inc., Frederick, Maryland, USA.
  • Gregory PD; Sangamo BioSciences, Inc., Richmond, California, USA.
  • Urnov FD; Sangamo BioSciences, Inc., Richmond, California, USA.
  • Malech HL; Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
Nat Biotechnol ; 34(4): 424-9, 2016 Apr.
Article en En | MEDLINE | ID: mdl-26950749
ABSTRACT
Gene therapy with genetically modified human CD34(+) hematopoietic stem and progenitor cells (HSPCs) may be safer using targeted integration (TI) of transgenes into a genomic 'safe harbor' site rather than random viral integration. We demonstrate that temporally optimized delivery of zinc finger nuclease mRNA via electroporation and adeno-associated virus (AAV) 6 delivery of donor constructs in human HSPCs approaches clinically relevant levels of TI into the AAVS1 safe harbor locus. Up to 58% Venus(+) HSPCs with 6-16% human cell marking were observed following engraftment into mice. In HSPCs from patients with X-linked chronic granulomatous disease (X-CGD), caused by mutations in the gp91phox subunit of the NADPH oxidase, TI of a gp91phox transgene into AAVS1 resulted in ∼15% gp91phox expression and increased NADPH oxidase activity in ex vivo-derived neutrophils. In mice transplanted with corrected HSPCs, 4-11% of human cells in the bone marrow expressed gp91phox. This method for TI into AAVS1 may be broadly applicable to correction of other monogenic diseases.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Terapia Genética / Trasplante de Células Madre Hematopoyéticas / Antígenos CD34 / Enfermedad Granulomatosa Crónica Límite: Animals / Humans Idioma: En Revista: Nat Biotechnol Asunto de la revista: BIOTECNOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
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PubMed Links
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Células Madre Hematopoyéticas / Terapia Genética / Trasplante de Células Madre Hematopoyéticas / Antígenos CD34 / Enfermedad Granulomatosa Crónica Límite: Animals / Humans Idioma: En Revista: Nat Biotechnol Asunto de la revista: BIOTECNOLOGIA Año: 2016 Tipo del documento: Article País de afiliación: Estados Unidos