共 31 条
A lentiviral vector encoding the human Wiskott Aldrich syndrome protein corrects immune and cytoskeletal defects in WASP knockout mice
被引:97
作者:

Charrier, S
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机构: Genethon, CNRS, UMR 8115, F-91002 Evry, France

Stockholm, D
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h-index: 0
机构: Genethon, CNRS, UMR 8115, F-91002 Evry, France

Seye, K
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h-index: 0
机构: Genethon, CNRS, UMR 8115, F-91002 Evry, France

Opolon, P
论文数: 0 引用数: 0
h-index: 0
机构: Genethon, CNRS, UMR 8115, F-91002 Evry, France

Taveau, M
论文数: 0 引用数: 0
h-index: 0
机构: Genethon, CNRS, UMR 8115, F-91002 Evry, France

Gross, DA
论文数: 0 引用数: 0
h-index: 0
机构: Genethon, CNRS, UMR 8115, F-91002 Evry, France

Bucher-Laurent, S
论文数: 0 引用数: 0
h-index: 0
机构: Genethon, CNRS, UMR 8115, F-91002 Evry, France

Delenda, C
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h-index: 0
机构: Genethon, CNRS, UMR 8115, F-91002 Evry, France

Vainchenker, W
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h-index: 0
机构: Genethon, CNRS, UMR 8115, F-91002 Evry, France

Danos, O
论文数: 0 引用数: 0
h-index: 0
机构: Genethon, CNRS, UMR 8115, F-91002 Evry, France

Galy, A
论文数: 0 引用数: 0
h-index: 0
机构: Genethon, CNRS, UMR 8115, F-91002 Evry, France
机构:
[1] Genethon, CNRS, UMR 8115, F-91002 Evry, France
[2] Inst Gustave Roussy, INSERM, U362, F-94805 Villejuif, France
关键词:
lentiviral vector;
Wiskott-Aldrich syndrome;
bone marrow;
transplantation;
dendritic cells;
D O I:
10.1038/sj.gt.3302440
中图分类号:
Q5 [生物化学];
Q7 [分子生物学];
学科分类号:
071010 ;
081704 ;
摘要:
Wiskott - Aldrich syndrome ( WAS) is an immune deficiency with thrombopenia resulting from mutations in the WASP gene. This gene normally encodes the Wiskott - Aldrich syndrome protein ( WASP), a major cytoskeletal regulator expressed in hematopoietic cells. Gene therapy is a promising option for the treatment of WAS, requiring that clinically applicable WASP gene transfer vectors demonstrate efficacy in preclinical studies. Here, we describe a self-inactivating HIV-1-derived lentiviral vector encoding human WASP and show that it effectively transduced bone marrow progenitor cells of WASP knockout (WKO) mice. Transplantation of these transduced cells into lethally irradiated WKO recipients led to stable expression of WASP and correction of immune, inflammatory and cytoskeletal defects. Splenic T-cell proliferation was restored, podosomes were reinstated on bone-marrow-derived dendritic cells and colon inflammation was reduced. This shows for the first time ( a) that cytoskeletal defects can be corrected in WKO mice, ( b) that human WASP is biologically active in mice and ( c) that a lentiviral vector is effective to express human WASP in vivo over several months. These data support further development of such lentiviral vectors for the gene therapy of WAS.
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页码:597 / 606
页数:10
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