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Prepublished online as a Blood First Edition Paper on June 21, 2002; DOI 10.1182/blood-2002-04-1245. This Article Full Text (PDF) All Versions of this Article: 2002-04-1245v1 100/8/2732    most recent Alert me when this article is cited Alert me if a correction is posted 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 Galimi, F. Articles by Verma, I. M Search for Related Content PubMed PubMed Citation Articles by Galimi, F. Articles by Verma, I. M Social Bookmarking                   What's this? Submitted April 26, 2002 Accepted June 1, 2002 Gene therapy of Fanconi anemia: preclinical efficacy using lentiviral vectors Francesco Galimi, Meenakshi Noll, Yoshiyuki Kanazawa, Timothy Lax, Cynthia Chen, Markus Grompe, and Inder M Verma* Laboratory of Genetics, The Salk Institute, La Jolla, CA, USA Department of Molecular and Medical Genetics, Oregon Health Science University, Portland, OR, USA * Corresponding author; email: verma{at}salk.edu. Fanconi anemia (FA) is an inherited cancer susceptibility syndrome due to mutations in a DNA repair pathway including at least six genes (FANCA, FANCC, FANCD2, FANCE, FANCF, and FANCG). The clinical course of the disease is dominated by progressive, life-threatening bone marrow failure, and high incidence of acute myelogenous leukemia and solid tumors. Allogeneic bone marrow transplantation (BMT) is a therapeutic option, but requires HLA-matched donors. Gene therapy holds great promise for FA, but previous attempts to use retroviral vectors in humans have proven ineffective, given the impaired proliferation potential of human FA hematopoietic progenitors (HPCs). In this work, we show that using lentiviral vectors efficient genetic correction can be achieved in quiescent hematopoietic progenitors from fanca-/- and fancc-/- mice. Long-term repopulating HPCs were transduced by a single exposure of unfractionated bone marrow mononuclear cells to lentivectors carrying the normal gene. Notably, no cell purification or cytokine prestimulation was necessary. Resistance to DNA-damaging agents was fully restored by lentiviral transduction, allowing for in vivo selection of the corrected cells with non-ablative doses of cyclophosphamide. This study strongly supports the use of lentiviral vectors for FA gene therapy in humans. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Si, A. C. Pulliam, Y. Linka, S. Ciccone, C. Leurs, J. Yuan, O. Eckermann, S. Fruehauf, S. Mooney, H. Hanenberg, et al. Overnight transduction with foamyviral vectors restores the long-term repopulating activity of Fancc-/- stem cells Blood, December 1, 2008; 112(12): 4458 - 4465. [Abstract] [Full Text] [PDF] P. Blancafort, M. P. Tschan, S. Bergquist, D. Guthy, A. Brachat, D. A. Sheeter, B. E. Torbett, D. Erdmann, and C. F. Barbas III Modulation of drug resistance by artificial transcription factors Mol. Cancer Ther., March 1, 2008; 7(3): 688 - 697. [Abstract] [Full Text] [PDF] H. Ly, Y. Kawase, R. Yoneyama, and R. J. Hajjar Gene Therapy in the Treatment of Heart Failure Physiology, April 1, 2007; 22(2): 81 - 96. [Abstract] [Full Text] [PDF] A. Mankad, T. Taniguchi, B. Cox, Y. Akkari, R. K. Rathbun, L. Lucas, G. Bagby, S. Olson, A. D'Andrea, and M. 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