dc.creator | Morianos, I. | en |
dc.creator | Siapati, E. K. | en |
dc.creator | Pongas, G. | en |
dc.creator | Vassilopoulos, G. | en |
dc.date.accessioned | 2015-11-23T10:39:53Z | |
dc.date.available | 2015-11-23T10:39:53Z | |
dc.date.issued | 2012 | |
dc.identifier | 10.1038/gt.2011.98 | |
dc.identifier.issn | 0969-7128 | |
dc.identifier.uri | http://hdl.handle.net/11615/31130 | |
dc.description.abstract | beta-Globin locus control region (LCR) sequences have been widely used for the regulated expression of the human beta-globin gene in therapeutic viral vectors. In this study, we compare the expression of the human beta-globin gene from either the HS2/HS3 beta-globin LCR or the HS40 regulatory element from the alpha-globin locus in the context of foamy virus (FV) vectors for the genetic correction of beta-thalassemia. Both regulatory elements expressed comparable levels of human beta-globin in a murine erythroleukemic line, whereas in murine hematopoietic stem cells the HS40.beta vector proved more efficient in beta-globin expression and correction of the beta-thalassemia phenotype. Following transplantation in the Hbb(th3/+) mouse model, the expression efficiency by the two vectors was similar, whereas the HS40.beta 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 beta-globin expression and restoration of the thalassemic phenotype as evidenced by enhanced erythropoiesis and decreased apoptosis. Our data suggest that FV vectors with the alpha-globin HS40 element can be used as alternative but equally efficient vehicles for human beta-globin gene expression for the genetic correction of beta-thalassemia. Gene Therapy (2012) 19, 303-311; doi:10.1038/gt.2011.98; published online 7 July 2011 | en |
dc.source.uri | <Go to ISI>://WOS:000301355800009 | |
dc.subject | beta-globin | en |
dc.subject | foamy virus | en |
dc.subject | thalassemia | en |
dc.subject | HS40 | en |
dc.subject | HEMATOPOIETIC STEM-CELLS | en |
dc.subject | LOCUS-CONTROL REGION | en |
dc.subject | FOAMY VIRUS VECTORS | en |
dc.subject | BONE-MARROW-TRANSPLANTATION | en |
dc.subject | TRANSGENIC MICE | en |
dc.subject | PHENOTYPIC CORRECTION | en |
dc.subject | EXPRESSION | en |
dc.subject | THERAPY | en |
dc.subject | ACTIVATION | en |
dc.subject | HEMOGLOBINOPATHIES | en |
dc.subject | Biochemistry & Molecular Biology | en |
dc.subject | Biotechnology & Applied Microbiology | en |
dc.subject | Genetics & Heredity | en |
dc.subject | Medicine, Research & Experimental | en |
dc.title | Comparative analysis of FV vectors with human alpha- or beta-globin gene regulatory elements for the correction of beta-thalassemia | en |
dc.type | journalArticle | en |