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Gene therapy of beta-thalassemia Gene therapy is a therapeutic technique by which a functioning gene is inserted into the somatic cells of a patient to correct a genetic error or to provide a new function to the cell. Since 1989 we pioneered the use of retroviral vector-mediated gene transfer for gene therapy of hematopoietic genetic diseases. Correction of genetic disorders affecting the progeny of multipotent stem cells requires integration of a therapeutic gene in undifferentiated, self-renewing stem cells and regulation of its expression in specific, differentiated cells. Globin gene transfer for the treatment of hemoglobinopathies represents a relevant model in which to study strategies aimed at transducing hematopoietic stem cells (HSCs) and restrict transgene expression to a single differentiated cell lineage. We recently developed lentiviral vectors with lineage-specific transcriptional activity to express the human beta-globin gene. Correction of thalassemia was achieved in murine preclinical models by transplanting genetically-corrected hematopoietic stem cells. Ongoing projects in the laboratory are focused on: 1) gene transfer and correction of human hematopoietic progenitors, obtained from bone marrow of thalassemic patients; 2) phenotypic and biological characterization of CD34+ cells from thalassemic patients; 3) analysis of vector integration profile in human genome and long-range effect on gene expression.
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