Hemoglobin subunit beta gene (HBB)

The Hemoglobin subunit beta (HBB) gene, located on chromosome 11, encodes the beta-globin protein, which is an essential component of adult hemoglobin (HbA) responsible for oxygen transport in red blood cells (NCBI Gene ID: 3043). Mutations in this gene are the underlying cause of major hemoglobinopathies, including sickle cell disease and beta-thalassemia, which result from either structural defects or deficient production of the beta-globin chain (UniProt P68871). In the context of hematopoietic stem and progenitor cell (HSPC) genomic DNA, the HBB gene is a primary target for curative gene therapies that aim to correct or supplement the defective genetic sequence. Therapeutic approaches such as betibeglogene autotemcel and lovotibeglogene autotemcel involve the ex vivo delivery of functional HBB gene copies into HSPCs using lentiviral vectors (FDA, 2022; FDA, 2023). Once these modified stem cells engraft in the bone marrow, they produce a progeny of red blood cells capable of synthesizing functional hemoglobin, thereby alleviating the clinical manifestations of the disease. This target is central to the development of precision medicine and gene-editing technologies, including CRISPR/Cas9, which are being explored to directly repair HBB mutations in situ.

Other names

Beta-globin geneHBB locusHemoglobin beta chain geneHBDCD113t-C

Ex vivo gene addition using lentiviral vectors to deliver a functional or modified HBB gene into hematopoietic stem cells, or direct genomic correction using site-specific endonucleases to restore functional beta-globin production.