HBB gene mutation affects the synthesis of β-globin, resulting in an imbalance of α-globin and β-globin, which in turn leads to erythropoiesis disorders and hemolytic anemia.
At present, the routine treatment of patients with transfusion-dependent β-thalassemia (TDT) is regular blood transfusion and iron chelation. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been the only curative therapy for transfusion-dependent β-thalassemia (TDT) for decades. However, the difficulty of finding HLA-matched donors and the risk of graft versus host disease (GVHD) greatly limit the implementation of allo-HSCT.
The treatment of β-thalassemia with gene therapy involves ex vivo gene transfer of functional β-globin to autologous hematopoietic stem cells(HSCs). These cells are harvested from bone marrow or from mobilized peripheral blood of the patient. The HSCs are cultured ex vivo and then are subjected to gene transfer with an integrating lentiviral vector encoding functional β-globin. Unlike allo-HSCT, gene therapy does not require HLA-matched donors and greatly reduce the risk of GVHD. Gene therapy can be as effective as the bone marrow transplant in achieving once in a lifetime cure, bringing hope to patients.
