Hemoglobin subunit beta gene locus (HBB) (HBB)

The Hemoglobin subunit beta (HBB) gene locus, located on chromosome 11p15.4, provides the essential genetic instructions for synthesizing the beta-globin protein, which is a critical component of adult hemoglobin (HbA) (UniProt P68871). In hematopoietic stem cells (HSCs), mutations within this locus are the primary cause of major hemoglobinopathies, such as sickle cell disease and beta-thalassemia, which result from structural abnormalities or reduced production of beta-globin (NIH MedlinePlus). Therapeutic strategies targeting the HBB locus in HSCs aim to restore functional hemoglobin production through ex vivo genetic modification. This is typically achieved by using lentiviral vectors to introduce a functional HBB gene (gene addition) or by employing precision tools like CRISPR/Cas9 to directly repair the underlying mutation (gene correction) (FDA Lyfgenia Summary; Nature Communications). Once these modified HSCs are re-infused into the patient, they engraft in the bone marrow and differentiate into red blood cells that produce healthy hemoglobin, potentially offering a one-time curative treatment for life-threatening blood disorders.

Other names

Beta-globin geneHBB locusHemoglobin beta chain geneBeta-globin cluster

Gene addition via lentiviral vector delivery of functional HBB cDNA; Gene correction via homology-directed repair (HDR) using CRISPR/Cas9 or base editing systems.