Beta-hemoglobinopathies are caused by mutations affecting the production of the adult hemoglobin beta-chain. Transplantation of autologous, genetically modified hematopoietic stem cells (HSCs) is an attractive therapeutic option for patients lacking a suitable allogeneic donor. Interestingly, persistence of fetal gamma-globin chain synthesis in adult life substantially ameliorates the clinical phenotype of beta-hemoglobinopathy patients. Dr. Miccio will discuss how the knowledge of the molecular mechanisms underlying beta- and gamma-globin gene regulation is instrumental to develop novel therapeutic approaches aimed at restoring gamma-globin expression in patients affected by beta-hemoglobinopathies. She will also discuss novel genome editing-based strategies aimed at correcting patient HSCs for the treatment of beta-hemoglobinopathies.