A zinc - finger transcriptional activator designed to interact with the γ - globin gene promoters enhances fetal hemoglobin production in primary human adult erythroblasts Running Title : Zinc finger - mediated induction of fetal hemoglobin
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چکیده
Fetal hemoglobin is a potent genetic modifier of the severity of β-thalassemia and sickle cell anemia. We utilized an in vitro culture model of human erythropoiesis in which late stage erythroblasts are derived directly from human CD34 + hematopoietic cells to evaluate HbF production. This system recapitulates expression of globin genes according to the developmental stage of the originating cell source. When cytokine-mobilized peripheral blood
منابع مشابه
Induction of Fetal Hemoglobin In Vivo Mediated by a Synthetic γ-Globin Zinc Finger Activator
Sickle cell disease (SCD) and β-thalassemia patients are phenotypically normal if they carry compensatory hereditary persistence of fetal hemoglobin (HPFH) mutations that result in increased levels of fetal hemoglobin (HbF, γ-globin chains) in adulthood. Thus, research has focused on manipulating the reactivation of γ-globin gene expression during adult definitive erythropoiesis as the most pro...
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β-Thalassemia major results from severely reduced or absent expression of the β-chain of adult hemoglobin (α₂β₂;HbA). Increased levels of fetal hemoglobin (α₂γ₂;HbF), such as occurs with hereditary persistence of HbF, ameliorate the severity of β-thalassemia, raising the potential for genetic therapy directed at enhancing HbF. We used an in vitro model of human erythropoiesis to assay for enhan...
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تاریخ انتشار 2010