Fetal hemoglobin expression via HBG1 and HBG2 promoter modification

The "Fetal hemoglobin expression via HBG1/2 promoter modification" target refers specifically to the genomic DNA regulatory regions upstream of the human gamma-globin genes (HBG1 and HBG2), which encode components of fetal hemoglobin (HbF). In adults, these genes are normally silenced by transcriptional repressors such as BCL11A. Genome-editing strategies—most notably using CRISPR/Cas9—disrupt or modify specific motifs within these promoters that are bound by repressors. This reactivation leads to increased HbF production in red blood cell precursors. Elevated HbF can compensate for defective adult β-globin chains in disorders like sickle cell disease and β-thalassemia, making this approach a promising therapeutic strategy. Editing is typically performed ex vivo on patient-derived hematopoietic stem/progenitor cells before transplantation back into patients. Preclinical studies show efficient induction of HbF with minimal off-target effects or impairment in multilineage differentiation potential after transplantation into animal models[1][2].

Other names

γ-globin gene promoter modificationHBG1/HBG2 promoter editingFetal hemoglobin (HbF) induction via γ-globin promotersReactivation of fetal hemoglobin by HBG1/HBG2 editing

Disruption or modification of the BCL11A binding site in the HBG1/HBG2 promoters to relieve repression and reactivate γ-globin gene expression, leading to increased fetal hemoglobin production[1][2]