Beta-globin gene locus (HBB locus)

The beta-globin gene locus, located on chromosome 11p15.4, is a cluster of genes including HBB, which encodes the beta-subunit of adult hemoglobin (HbA) (NIH, 2023). In autologous CD34+ hematopoietic stem cells, this locus serves as a primary target for gene therapy to treat hereditary hemoglobinopathies like beta-thalassemia and sickle cell disease (PubMed, 2022). Current therapeutic interventions, such as betibeglogene autotemcel, utilize lentiviral vectors to insert a functional HBB gene into the patient's own stem cells ex vivo (FDA, 2022). These modified cells are then re-infused, where they produce functional hemoglobin, potentially eliminating the need for lifelong blood transfusions (StatPearls, 2023). Safety considerations for targeting this locus include the risk of insertional mutagenesis and the toxicities associated with the required myeloablative conditioning (PubMed, 2021).

Other names

Hemoglobin subunit beta locusHBB gene clusterBeta-globin cluster11p15.4 locusβ-globin locus

Lentiviral vector-mediated gene addition of a functional beta-globin gene into autologous hematopoietic stem cells to restore production of adult hemoglobin.