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Blood, 15 December 2007, Vol. 110, No. 13, pp. 4175-4178. Prepublished online as a Blood First Edition Paper on October 5, 2007; DOI 10.1182/blood-2007-08-108647. This Article Full Text Full Text (PDF) Supplemental Methods and Figure All Versions of this Article: blood-2007-08-108647v1 110/13/4175    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 Lisowski, L. Articles by Sadelain, M. Search for Related Content PubMed PubMed Citation Articles by Lisowski, L. Articles by Sadelain, M. Related Collections Brief Reports Gene Therapy Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  GENE THERAPY Brief Report Locus control region elements HS1 and HS4 enhance the therapeutic efficacy of globin gene transfer in β-thalassemic mice Leszek Lisowski1,2, and Michel Sadelain1 1 Center for Cell Engineering, Gene Transfer and Somatic Cell Engineering Laboratory, Department of Medicine, and Molecular Pharmacology and Chemistry Program, Memorial Sloan-Kettering Cancer Center, New York, NY; and 2 Cell Biology and Genetics Graduate Program, Weill Graduate School of Medical Sciences, Cornell University, New York, NY Globin gene transfer in autologous hematopoietic stem cells is a promising therapeutic option for subjects with β-thalassemia major. In this approach, high level, erythroid-specific globin transgene expression should correct ineffective erythropoiesis and hemolytic anemia following the delivery of only 1 to 2 vector copies per cell. The generation of vectors that provide high-level globin expression and require low vector copy (VC) integration is therefore essential for both safety and efficacy. We show here the major roles played by 2 lesser-known locus control region elements, termed HS1 and HS4. Partial deletions within HS4 markedly reduce in vivo globin expression requiring multiple VC per cell to correct the anemia. Most strikingly, addition of HS1 to HS2-3-4 increases globin expression by 52%, yielding 9 g Hb/VC in β-thalassemic mice. Thus, while vectors encoding HS2-3-4 provide curative levels of hemoglobin at 1 to 2 copies per cell, adding HS1 is a promising alternative strategy if upcoming clinical trials prove higher levels of expression to be necessary. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Miccio, R. Cesari, F. Lotti, C. Rossi, F. Sanvito, M. Ponzoni, S. J. E. Routledge, C.-M. Chow, M. N. Antoniou, and G. Ferrari In vivo selection of genetically modified erythroblastic progenitors leads to long-term correction of {beta}-thalassemia PNAS, July 29, 2008; 105(30): 10547 - 10552. [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]

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