Genetically Modified Hematopoietic Stem Cells for Gene Therapy in Beta-Thalassemia: Power of Viral Vector Towards Clinical Application

Β-thalassemia is a genetic disorder resulting from defects in the Β-globin gene. Patients having a compatible human leukocyte antigen (HLA) matched donor can be cured by transplantation of allogeneic hematopoietic stem cells (HSCs). However, some recipients have a high risk of morbidity/mortality due to graft versus host disease (GVHD) or graft rejection. Importantly, most patients do not have such HLA matchrelated donor issues. Thus, the infusion of autologous HSCs modified with a lentiviral vector expressing the Β-globin therapeutic gene in the erythroid progenitors is a promising approach to fully cure the disease. Here we review the history of Β-thalassemia treatment, particularly the development of the Β-globin lentiviral vector, with emphasis on clinical applications and future perspectives in a new era of medicine.