biostudies-literatureUnknown17(1)Goswami SG<h4>Background</h4>Hereditary persistence of Fetal Hemoglobin (HPFH) is a benign condition known to mitigate symptoms in individuals with co-inherited β-hemoglobinopathies, such as β-thalassemia (BT) and sickle cell disease (SCD), through the reactivation of fetal hemoglobin (HbF). HPFH typically arises from deletions of varying sizes affecting the β-globin gene cluster or point mutations in the promoters of the γ-globin genes. While the therapeutic benefits of point mutations have been extensively studied, the potential of deletional forms of HPFH remains underexplored in preclinical settings.<h4>Method</h4>In this study, we generated benign deletional HPFH3 genotype in SCD and BT patient-derived HSPCs using CRISPR/Cas9 and showed that therapeutically relevant levels of HbF reactivation rStem cell research & therapy46https://www.ebi.ac.uk/biostudies/studies/S-EPMC12836809biostudies-literatureCRISPR editing of HPFH3 genotype induces γ-globin expression and reverses sickle cell disease and β-thalassemia phenotypes.PMC12836809Jain SMehta PRamalingam SGoswami SGBhargava NIyer ARBajaj ASaravanakumar VGunda PNakamura YKurita RArvinden VRJha SKSingh PSingh SKumar AGupta PYadav PfalseCRISPR editing of HPFH3 genotype induces γ-globin expression and reverses sickle cell disease and β-thalassemia phenotypes.<h4>Background</h4>Hereditary persistence of Fetal Hemoglobin (HPFH) is a benign condition known to mitigate symptoms in individuals with co-inherited β-hemoglobinopathies, such as β-thalassemia (BT) and sickle cell disease (SCD), through the reactivation of fetal hemoglobin (HbF). HPFH typically arises from deletions of varying sizes affecting the β-globin gene cluster or point mutations in the promoters of the γ-globin genes. While the therapeutic benefits of point mutations have been extensively studied, the potential of deletional forms of HPFH remains underexplored in preclinical settings.<h4>Method</h4>In this study, we generated benign deletional HPFH3 genotype in SCD and BT patient-derived HSPCs using CRISPR/Cas9 and showed that therapeutically relevant levels of HbF reactivation r2025-01-01T00:00:00Z2025 Dec2026-06-15T03:17:24.029Z2026-06-15T03:11:16.422ZS-EPMC128368094142362110.1186/s13287-025-04582-1