期刊
GENE THERAPY
卷 12, 期 7, 页码 597-606出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.gt.3302440
关键词
lentiviral vector; Wiskott-Aldrich syndrome; bone marrow; transplantation; dendritic cells
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据