Hemoglobin subunit beta (HBB) gene in autologous CD34+ hematopoietic stem cells (HBB)

The Hemoglobin subunit beta (HBB) gene encodes the beta-globin protein, a critical component of the adult hemoglobin tetramer (HbA) responsible for oxygen transport in red blood cells [UniProt P68871]. Mutations in this gene lead to severe hemoglobinopathies, including sickle cell disease, caused by the HbS variant, and beta-thalassemia, characterized by reduced or absent beta-globin production [NIH MedlinePlus, 2022]. In therapeutic contexts involving autologous CD34+ hematopoietic stem cells (HSCs), the HBB gene is the primary target for gene addition therapies designed to provide a functional genetic template for hemoglobin synthesis. Drugs such as betibeglogene autotemcel and lovotibeglogene autotemcel utilize lentiviral vectors to deliver a functional HBB transgene (often a modified version like HbA-T87Q) into the patient's own harvested stem cells [FDA Zynteglo Label, 2022; FDA Lyfgenia Label, 2023]. Following myeloablative conditioning, these modified HSCs engraft in the bone marrow and differentiate into mature erythrocytes that produce therapeutic levels of hemoglobin, thereby reducing or eliminating the clinical manifestations of the underlying disease. This approach addresses the root genetic cause of the disorder by enabling the patient's own hematopoietic system to produce healthy red blood cells. Monitoring efficacy typically involves measuring the levels of therapeutic hemoglobin produced by the modified cells and assessing the vector copy number within the cell population [PubMed 29669226].

Other names

Beta-globin geneHemoglobin beta chainHBBCD34+ HSCs expressing HBBAutologous CD34+ cells encoding the HBB gene

Ex vivo lentiviral vector-mediated gene addition of a functional or modified HBB gene into autologous CD34+ hematopoietic stem cells, which are then re-infused into the patient to restore production of functional adult hemoglobin.