期刊
BLOOD
卷 112, 期 12, 页码 4458-4465出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2007-07-102947
关键词
-
类别
资金
- National Institutes of Health (Bethesda, MD) [PPG-P01-HL533586]
- Deutsche Forschungsgemeinschaft (Bonn, Germany) [SPP1230]
- Riley Children's Foundation (Indianapolis, IN)
- Indiana University NCI-designated Cancer Center (Indianapolis, IN)
Fanconi anemia (FA) is a complex genetic disorder characterized by congenital abnormalities, bone marrow failure, and myeloid malignancies. Identification of 13 FA genes has been instrumental to explore gene transfer technologies aimed at correction of autologous FA-deficient stem cells. To date, 3 human FA stem cell gene therapy trials with standard 4-day transduction protocols using gammaretroviral vectors failed to provide clinical benefit. In addition, 2- to 4 day ex vivo manipulation of bone marrow from mice containing a disruption of the homologue of human FANCC (Fancc) results in a timedependent increase in apoptosis and a risk for malignant transformation of hematopoietic cells. Here, we show that a 14-hour transduction period allows a foamyviral vector construct expressing the human FANCC cDNA to efficiently transduce murine FA stem cells with 1 to 2 proviral integrations per genome. Functionally, the repopulating activity of Fancc(-/-) stem cells from reconstituted mice expressing the recombinant FANCC transgene was comparable with wild-type controls. Collectively, these data provide evidence that short-term transduction of c-kit(+) cells with a foamyviral vector is sufficient for functional correction of a stem cell phenotype in a murine FAmodel. These data could have implications for future gene therapy trials for FA patients. (Blood. 2008;112:4458-4465)
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