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Prepublished online as a Blood First Edition Paper on October 31, 2002; DOI 10.1182/blood-2002-07-2211. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-07-2211v1 101/6/2175    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 Persons, D. A. Articles by Nienhuis, A. W. Search for Related Content PubMed PubMed Citation Articles by Persons, D. A. Articles by Nienhuis, A. W. Related Collections Transplantation Gene Expression Gene Therapy Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 March 2003, Vol. 101, No. 6, pp. 2175-2183 GENE THERAPY The degree of phenotypic correction of murine -thalassemia intermedia following lentiviral-mediated transfer of a human -globin gene is influenced by chromosomal position effects and vector copy number Derek A. Persons, Phillip W. Hargrove, Esther R. Allay, Hideki Hanawa, and Arthur W. Nienhuis From the Division of Experimental Hematology, Department of Hematology and Oncology, St Jude Children's Research Hospital, Memphis, TN. Increased fetal hemoglobin (HbF) levels diminish the clinical severity of -thalassemia and sickle cell anemia. A treatment strategy using autologous stem cell-targeted gene transfer of a -globin gene may therefore have therapeutic potential. We evaluated oncoretroviral- and lentiviral-based -globin vectors for expression in transduced erythroid cell lines. Compared with -globin, oncoretroviral vectors containing either a -spectrin or -globin promoter and the -globin HS40 element, a -globin lentiviral vector utilizing the -globin promoter and elements from the -globin locus control region demonstrated a higher probability of expression. This lentiviral vector design was evaluated in lethally irradiated mice that received transplants of transduced bone marrow cells. Long-term, stable erythroid expression of human -globin was observed with levels of vector-encoded -globin mRNA ranging from 9% to 19% of total murine -globin mRNA. The therapeutic efficacy of the vector was subsequently evaluated in a murine model of -thalassemia intermedia. The majority of mice that underwent transplantation expressed significant levels of chimeric m2h2 molecules (termed HbF), the amount of which correlated with the degree of phenotypic improvement. A group of animals with a mean HbF level of 21% displayed a 2.5 g/dL (25 g/L) improvement in Hb concentration and normalization of erythrocyte morphology relative to control animals. -Globin expression and phenotypic improvement was variably lower in other animals due to differences in vector copy number and chromosomal position effects. These data establish the potential of using a -globin lentiviral vector for gene therapy of -thalassemia. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: 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. 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