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Blood, 15 November 2005, Vol. 106, No. 10, pp. 3386-3395. Prepublished online as a Blood First Edition Paper on August 2, 2005; DOI 10.1182/blood-2004-12-4736. This Article Full Text (PDF) All Versions of this Article: 2004-12-4736v1 106/10/3386    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 Verhoeyen, E. Articles by Cosset, F.-L. Search for Related Content PubMed PubMed Citation Articles by Verhoeyen, E. Articles by Cosset, F.-L. Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 13, 2004 Accepted July 10, 2005 Novel lentiviral vectors displaying "early acting cytokines" selectively promote survival and transduction of NOD/SCID repopulating human hematopoietic stem cells Els Verhoeyen, Maciej Wiznerowicz, Delphine Olivier, Brigitte Izac, Didier Trono, Anne Dubart-Kupperschmitt, and Francois-Loic Cosset* Laboratoire de Vectorologie Retrovirale et Therapie Genique, INSERM U412, IFR128 BioSciences Lyon-Gerland, Ecole Normale Superieure de Lyon, Lyon, France Department of Microbiology and Molecular Medicine, Faculty of Medicine, University of Geneva, Geneva, Switzerland Hematology Department, INSERM U567, CNRS UMR 8104, Institut Cochin, Maternite de Port-Royal, Paris, France * Corresponding author; email: flcosset{at}ens-lyon.fr. A major limitation of current lentiviral vectors (LVs) is their inability to govern efficient gene transfer into quiescent cells, such as human CD34+ cells that reside into G0 phase of the cell cycle and that are highly enriched in hematopoietic stem cells. This hampers their application for gene therapy of hematopoietic cells. Here, we designed novel lentiviral vectors that overcome this restriction by displaying early-acting cytokines on their surface. Display of thrombopoietin, stem cell factor or both cytokines on LV surface allowed efficient gene delivery into quiescent cord blood CD34+ cells. Moreover, these surface-engineered LVs preferentially transduced and promoted survival of resting CD34+ cells rather than cycling cells. Finally, and most importantly, these novel LVs allowed superior gene transfer in the most immature CD34+ cells as compared to conventional LVs, even when the latter vectors were used to transduce cells in the presence of recombinant cytokines. This was demonstrated by their capacity to promote selective transduction of CD34+ cell in in vitro derived long-term culture initiating cell colonies (LTC-ICs) and of long-term NOD/ SCID repopulating cells (SRCs) in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Gene therapy: efficient targeting of hematopoietic stem cells Stefan Karlsson Blood 2005 106: 3333. [Full Text] [PDF] This article has been cited by other articles: H. Matsui, M. Shibata, B. Brown, A. Labelle, C. Hegadorn, C. Andrews, R. P. Hebbel, J. Galipeau, C. Hough, and D. Lillicrap Ex Vivo Gene Therapy for Hemophilia A That Enhances Safe Delivery and Sustained In Vivo Factor VIII Expression from Lentivirally Engineered Endothelial Progenitors Stem Cells, October 1, 2007; 25(10): 2660 - 2669. [Abstract] [Full Text] [PDF] Y.-W. Pan, J. M. Scarlett, T. T. Luoh, and P. Kurre Prolonged Adherence of Human Immunodeficiency Virus-Derived Vector Particles to Hematopoietic Target Cells Leads to Secondary Transduction In Vitro and In Vivo J. Virol., January 15, 2007; 81(2): 639 - 649. [Abstract] [Full Text] [PDF]

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