Clinical application of base editing for treating beta-thalassemia
Beta-Thalassemia is a genetic disease caused by reduced or absent beta-hemoglobin production. Base editing offers a precise way to correct gene mutations without causing harmful DNA breaks. We used a transformer base editor (tBE) to target a specific region in the HBG1/2 promoter, aiming to increase fetal hemoglobin (HbF) production in hematopoietic stem and progenitor cells (HSPCs) from both healthy donors and beta-thalassemia patients. In an early-phase clinical study, patients with beta-thalassemia received an infusion of their own CD34+ cells, edited with tBE to disrupt the same target in the HBG1/2 promoter; following this infusion, all patients, representing a range of beta-thalassemia genotypes, were able to discontinue red blood cell transfusions, achieving transfusion independence rapidly. Total hemoglobin and HbF concentrations increased significantly after treatment and remained stable or improved throughout the follow-up period, and the side effects observed were generally consistent with those expected from the pre-transplant conditioning regimen and autologous HSPC transplantation, with no deaths or cases of cancer reported.