Dr. Annarita Miccio
Sickle cell disease (SCD) is a genetic disease characterized by hemolytic anemia, pain crises, organ damage and reduced life expectancy. Despite the undeniable progress in the gene therapy field, the treatment of this disease requires further key improvements to achieve the full correction of the clinical phenotype. The clinical course of SCD is ameliorated by elevated levels of fetal γ-globins. In the frame of our DIM project, we have recently demonstrated that CRISPR/Cas9-mediated disruption of repressor binding sites in the γ-globin promoters in SCD patient hematopoietic stem/progenitor cell (HSPCs) efficiently reactivates fetal hemoglobin expression, and corrects the sickling cell phenotype. Here, we intend to set up a large-scale transfection system to genetically modify large numbers of HSPCs required for the reconstitution of a “healthy” hematopoietic system in SCD patients. This study will provide evidences of the efficacy and feasibility of our therapeutic strategy.
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