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Blood, 15 December 2003, Vol. 102, No. 13, pp. 4312-4319. Prepublished online as a Blood First Edition Paper on August 21, 2003; DOI 10.1182/blood-2003-04-1251. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 2003-04-1251v1 102/13/4312    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 Levasseur, D. N. Articles by Townes, T. M. Search for Related Content PubMed PubMed Citation Articles by Levasseur, D. N. Articles by Townes, T. M. Related Collections Hematopoiesis and Stem Cells Red Cells Transplantation Gene Therapy Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Correction of a mouse model of sickle cell disease: lentiviral/antisickling -globin gene transduction of unmobilized, purified hematopoietic stem cells Dana N. Levasseur, Thomas M. Ryan, Kevin M. Pawlik, and Tim M. Townes From the Department of Biochemistry and Molecular Genetics, Schools of Medicine and Dentistry, University of Alabama at Birmingham. Although sickle cell anemia was the first hereditary disease to be understood at the molecular level, there is still no adequate long-term treatment. Allogeneic bone marrow transplantation is the only available cure, but this procedure is limited to a minority of patients with an available, histocompatible donor. Autologous transplantation of bone marrow stem cells that are transduced with a stably expressed, antisickling globin gene would benefit a majority of patients with sickle cell disease. Therefore, the development of a gene therapy protocol that corrects the disease in an animal model and is directly translatable to human patients is critical. A method is described in which unmobilized, highly purified bone marrow stem cells are transduced with a minimum amount of self-inactivating (SIN) lentiviral vector containing a potent antisickling -globin gene. These cells, which were transduced in the absence of cytokine stimulation, fully reconstitute irradiated recipients and correct the hemolytic anemia and organ pathology that characterize the disease in humans. The mean increase of hemoglobin concentration was 46 g/L (4.6 g/dL) and the average lentiviral copy number was 2.2; therefore, a 21-g/L /vector copy increase (2.1-g/dL) was achieved. This transduction protocol may be directly translatable to patients with sickle cell disease who cannot tolerate current bone marrow mobilization procedures and may not safely be exposed to large viral loads. (Blood. 2003;102:4312-4319) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Gene therapy for sickle cell disease marches on David M. Bodine Blood 2003 102: 4247. [Full Text] [PDF] This article has been cited by other articles: Y. R. Su, J. L. Blakemore, Y. Zhang, M. F. Linton, and S. Fazio Lentiviral Transduction of ApoAI Into Hematopoietic Progenitor Cells and Macrophages: Applications to Cell Therapy of Atherosclerosis Arterioscler. Thromb. Vasc. Biol., August 1, 2008; 28(8): 1439 - 1446. [Abstract] [Full Text] [PDF] P. Moi and M. Sadelain Towards the genetic treatment of {beta}-thalassemia: new disease models, new vectors, new cells Haematologica, March 1, 2008; 93(3): 325 - 330. [Full Text] [PDF] L. 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