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Comparative analysis of FV vectors with human α- or β-globin gene regulatory elements for the correction of β-thalassemia

Gene Therapy volume 19, pages 303–311 (2012)Cite this article

Abstract

β-Globin locus control region (LCR) sequences have been widely used for the regulated expression of the human β-globin gene in therapeutic viral vectors. In this study, we compare the expression of the human β-globin gene from either the HS2/HS3 β-globin LCR or the HS40 regulatory element from the α-globin locus in the context of foamy virus (FV) vectors for the genetic correction of β-thalassemia. Both regulatory elements expressed comparable levels of human β-globin in a murine erythroleukemic line, whereas in murine hematopoietic stem cells the HS40.β vector proved more efficient in β-globin expression and correction of the β-thalassemia phenotype. Following transplantation in the Hbbth3/+ mouse model, the expression efficiency by the two vectors was similar, whereas the HS40.β vector achieved relatively more stable transgene expression. In addition, in an ex vivo assay using CD34+ cells from thalassemic patients, both vectors achieved significant human β-globin expression and restoration of the thalassemic phenotype as evidenced by enhanced erythropoiesis and decreased apoptosis. Our data suggest that FV vectors with the α-globin HS40 element can be used as alternative but equally efficient vehicles for human β-globin gene expression for the genetic correction of β-thalassemia.

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Acknowledgements

We thank Dr G Stamatoyannopoulos, Q Li and D Emery from the University of Washington (Seattle, WA) for the HS40 plasmid; Dr N Anagnou for providing the Hbbth3/+ mice; and Drs E Gouseti, S Grafako and A Kattamis (Children's Hospital, Agia Sofia, Athens, Greece) for providing β-thalassemia patient samples. The work was supported from an EU grant (CONSERT LSHB-CT-2004-005242) and a grant from the Greek GSRT (PENED 603).

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Authors and Affiliations

  1. Division of Genetics and Gene Therapy, Basic Research II, Biomedical Research Foundation of the Academy of Athens, Athens, Greece

    I Morianos, E K Siapati, G Pongas & G Vassilopoulos

  2. Division of Hematology, University of Thessaly Medical School, Larissa, Greece

    G Vassilopoulos

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  1. I Morianos
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  2. E K Siapati
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Correspondence to G Vassilopoulos.

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Morianos, I., Siapati, E., Pongas, G. et al. Comparative analysis of FV vectors with human α- or β-globin gene regulatory elements for the correction of β-thalassemia. Gene Ther 19, 303–311 (2012). https://doi.org/10.1038/gt.2011.98

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