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Blood, 1 June 2004, Vol. 103, No. 11, pp. 4062-4069.
Prepublished online as a Blood First Edition Paper on February 19, 2004; DOI 10.1182/blood-2004-01-0045.
 Previous Article | Table of Contents | Next Article 
GENE THERAPY
Efficient gene transfer into rhesus repopulating hematopoietic stem cells using a simian immunodeficiency virus–based lentiviral vector system
Hideki Hanawa,
Peiman Hematti,
Keyvan Keyvanfar,
Mark E. Metzger,
Allen Krouse,
Robert E. Donahue,
Steve Kepes,
John Gray,
Cynthia E. Dunbar,
Derek A. Persons, and
Arthur W. Nienhuis
From the Experimental Hematology Division, Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN; and Hematology Branch, National Heart, Lung, and Blood Institute (NHBLI), National Institutes of Health (NIH), Bethesda, MD.
High-titer, HIV-1–based lentiviral vector particles were found to transduce cytokine-mobilized rhesus macaque CD34+ cells and clonogenic progenitors very poorly (< 1%), reflecting the postentry restriction in rhesus cells to HIV infection. To overcome this barrier, we developed a simian immunodeficiency virus (SIV)–based vector system. A single exposure to a low concentration of amphotropic pseudotyped SIV vector particles encoding the green fluorescent protein (GFP) resulted in gene transfer into 68% ± 1% of rhesus bulk CD34+ cells and 75% ± 1% of clonogenic progenitors. Polymerase chain reaction (PCR) analysis of DNA from individual hematopoietic colonies confirmed these relative transduction efficiencies. To evaluate SIV vector–mediated stem cell gene transfer in vivo, 3 rhesus macaques underwent transplantation with transduced, autologous cytokine-mobilized peripheral blood CD34+ cells following myeloablative conditioning. Hematopoietic reconstitution was rapid, and an average of 18% ± 8% and 15% ± 7% GFP-positive granulocytes and monocytes, respectively, were observed 4 to 6 months after transplantation, consistent with the average vector copy number of 0.19 ± 0.05 in peripheral blood leukocytes as determined by real-time PCR. Vector insertion site analysis demonstrated polyclonal reconstitution with vector-containing cells. SIV vectors appear promising for evaluating gene therapy approaches in nonhuman primate models.
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