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Blood, 1 December 2008, Vol. 112, No. 12, pp. 4458-4465. Prepublished online as a Blood First Edition Paper on August 6, 2008; DOI 10.1182/blood-2007-07-102947. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-07-102947v1 112/12/4458    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Si, Y. Articles by Clapp, D. W. Search for Related Content PubMed PubMed Citation Articles by Si, Y. Articles by Clapp, D. W. Related Collections Hematopoiesis and Stem Cells Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Overnight transduction with foamyviral vectors restores the long-term repopulating activity of Fancc–/– stem cells Yue Si*,1,2, Anna C. Pulliam*,1,2, Yvonne Linka3, Samantha Ciccone1,2, Cordula Leurs3, Jin Yuan1,2, Olaf Eckermann3, Stefan Fruehauf4, Sean Mooney5,6, Helmut Hanenberg2,3, and D. Wade Clapp1,2 Departments of1 Microbiology and Immunology and 2 Pediatrics, Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis; 3 Department of Pediatric Oncology, Hematology and Clinical Immunology, Children's Hospital, Heinrich Heine University, Duesseldorf, Germany; 4 Department of Internal Medicine III, University of Heidelberg, Heidelberg, Germany; and 5 Center for Computational Biology and Bioinformatics and 6 Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis 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 time-dependent 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 FA model. These data could have implications for future gene therapy trials for FA patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Rio, N. W. Meza, A. Gonzalez-Murillo, S. Navarro, L. Alvarez, J. Surralles, M. Castella, G. Guenechea, J. C. Segovia, H. Hanenberg, et al. In vivo proliferation advantage of genetically corrected hematopoietic stem cells in a mouse model of Fanconi anemia FA-D1 Blood, December 15, 2008; 112(13): 4853 - 4861. [Abstract] [Full Text] [PDF]

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