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Blood, 28 May 2009, Vol. 113, No. 22, pp. 5434-5443. Prepublished online as a Blood First Edition Paper on April 1, 2009; DOI 10.1182/blood-2008-10-185199. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2008-10-185199v1 113/22/5434    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 Google Scholar Articles by Kim, Y.-J. Articles by Persons, D. A. PubMed PubMed Citation Articles by Kim, Y.-J. Articles by Persons, D. A. Related Collections Hematopoiesis and Stem Cells Transplantation Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Sustained high-level polyclonal hematopoietic marking and transgene expression 4 years after autologous transplantation of rhesus macaques with SIV lentiviral vector–transduced CD34+ cells Yoo-Jin Kim1,*, Yoon-Sang Kim2,*, Andre Larochelle1, Gabriel Renaud3, Tyra G. Wolfsberg3, Rima Adler1, Robert E. Donahue1, Peiman Hematti1, Bum-Kee Hong1, Jean Roayaei4, Keiko Akagi4, Janice M. Riberdy5, Arthur W. Nienhuis2, Cynthia E. Dunbar1,, and Derek A. Persons2, 1 Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Bethesda, MD; 2 Department of Hematology, St Jude Children's Research Hospital, Memphis, TN; 3 Genome Technology Branch, National Human Genome Research Institute, NIH, Bethesda, MD; 4 Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, Frederick, MD; and 5 Department of Immunology, St Jude Children's Research Hospital, Memphis, TN We previously reported that lentiviral vectors derived from the simian immunodeficiency virus (SIV) were efficient at transducing rhesus hematopoietic repopulating cells. To evaluate the persistence of vector-containing and -expressing cells long term, and the safety implications of SIV lentiviral vector–mediated gene transfer, we followed 3 rhesus macaques for more than 4 years after transplantation with transduced CD34+ cells. All 3 animals demonstrated significant vector marking and expression of the GFP transgene in T cells, B cells, and granulocytes, with mean GFP+ levels of 6.7% (range, 3.3%-13.0%), 7.4% (4.2%-13.4%), and 5.6% (3.1%-10.5%), respectively. There was no vector silencing in hematopoietic cells over time. Vector insertion site analysis of granulocytes demonstrated sustained highly polyclonal reconstitution, with no evidence for progression to oligoclonality. A significant number of clones were found to contribute at both 1-year and 3- or 4-year time points. No vector integrations were detected in the MDS1/EVI1 region, in contrast to our previous findings with a -retroviral vector. These data show that lentiviral vectors can mediate stable and efficient long-term expression in the progeny of transduced hematopoietic stem cells, with an integration profile that may be safer than that of standard Moloney murine leukemia virus (MLV)–derived retroviral vectors. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Naldini A Comeback for Gene Therapy Science, November 6, 2009; 326(5954): 805 - 806. [Abstract] [Full Text] [PDF] H. Zhao, T. I. Pestina, M. Nasimuzzaman, P. Mehta, P. W. Hargrove, and D. A. Persons Amelioration of murine {beta}-thalassemia through drug selection of hematopoietic stem cells transduced with a lentiviral vector encoding both {gamma}-globin and the MGMT drug-resistance gene Blood, June 4, 2009; 113(23): 5747 - 5756. [Abstract] [Full Text] [PDF]

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