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Prepublished online as a Blood First Edition Paper on August 21, 2003; DOI 10.1182/blood-2003-04-1251. This Article 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 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 Related Article in Blood Online Social Bookmarking                   What's this? Submitted May 2, 2003 Accepted August 5, 2003 Correction of a mouse model of sickle cell disease: lentiviral/anti-sickling -globin gene transduction of unmobilized, purified hematopoietic stem cells Dana N Levasseur, Thomas M Ryan, Kevin M Pawlik, and Tim M Townes* Department of Biochemistry and Molecular Genetics,Schools of Medicine and Dentistry, University of Alabama at Birmingham, Birmingham, AL, USA * Corresponding author; email: ttownes{at}uab.edu. 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, anti-sickling 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 anti-sickling -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 was 4.6 gms/dL and the average lentiviral copy number was 2.2; therefore, a 2.1 gm/dL/vector copy increase was achieved. This transduction protocol may be directly translatable to human sickle cell patients who cannot tolerate current bone marrow mobilization procedures and may not safely be exposed to large viral loads. 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