Hemoglobin subunit beta (HBB) genomic locus (HBB locus)

The Hemoglobin subunit beta (HBB) genomic locus, located on chromosome 11p15.4, encodes the beta-globin protein, which is a vital component of adult hemoglobin (HbA) responsible for oxygen transport [1]. This locus is the primary therapeutic target in hematopoietic stem and progenitor cells (HSPCs) for treating monogenic blood disorders like sickle cell disease (SCD) and beta-thalassemia [2]. In SCD, a specific point mutation in the HBB gene leads to the production of sickle hemoglobin (HbS), causing red blood cells to deform and obstruct blood flow [3]. Beta-thalassemia is characterized by various mutations in the HBB locus that reduce or eliminate beta-globin production, leading to severe anemia and the need for lifelong blood transfusions [4]. Therapeutic strategies targeting this locus in HSPCs involve ex vivo gene addition using lentiviral vectors or direct gene correction via CRISPR/Cas9 technology [5]. For example, lovotibeglogene autotemcel delivers a functional HBB gene into a patient's HSPCs, which then produce anti-sickling hemoglobin after being re-infused into the patient [6]. These therapies aim to provide a durable, one-time cure by ensuring that all subsequent generations of red blood cells derived from the modified HSPCs carry the corrected genetic information [7].

Other names

Beta-globin locusHemoglobin beta locus11p15.4 locusHBB gene

Gene addition via lentiviral vector-mediated delivery of a functional beta-globin gene or gene editing to correct endogenous mutations.