Disrupting ZBTB7A or BCL11A binding sites reactivates fetal hemoglobin in erythroblasts from healthy and β0-thalassemia/HbE individuals
1
Issued Date
2025-12-01
Resource Type
eISSN
20452322
Scopus ID
2-s2.0-105010598976
Journal Title
Scientific Reports
Volume
15
Issue
1
Rights Holder(s)
SCOPUS
Bibliographic Citation
Scientific Reports Vol.15 No.1 (2025)
Suggested Citation
Wongborisuth C., Innachai P., Saisawang C., Tubsuwan A., Jearawiriyapaisarn N., Kaewprommal P., Piriyapongsa J., Chiangjong W., Anurathapan U., Songdej D., Tangprasittipap A., Hongeng S. Disrupting ZBTB7A or BCL11A binding sites reactivates fetal hemoglobin in erythroblasts from healthy and β0-thalassemia/HbE individuals. Scientific Reports Vol.15 No.1 (2025). doi:10.1038/s41598-025-10791-8 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/111309
Title
Disrupting ZBTB7A or BCL11A binding sites reactivates fetal hemoglobin in erythroblasts from healthy and β0-thalassemia/HbE individuals
Corresponding Author(s)
Other Contributor(s)
Abstract
CRISPR/Cas9 genome editing has emerged as a promising treatment for genetic diseases like β-thalassemia. Editing γ-globin promoters to disrupt ZBTB7A/LRF or BCL11A binding sites has shown potential for reactivating fetal hemoglobin and treating sickle cell disease. However, its application to β<sup>0</sup>-thalassemia/HbE disease remains unclear. This study utilized CRISPR/Cas9 to disrupt these sites in mobilized CD34 + hematopoietic stem /progenitor cells from healthy donors and β<sup>0</sup>-thalassemia/HbE patients. The editing efficiency for the BCL11A site (75–92%) was higher than for the ZBTB7A/LRF site (57–60%). Both disruptions similarly increased fetal hemoglobin production in healthy donors (BCL11A 26.2 ± 1.4%, ZBTB7A/LRF 27.9 ± 1.5%) and β<sup>0</sup>-thalassemia/HbE cells (BCL11A 62.7 ± 0.9%, ZBTB7A/LRF 64.0 ± 1.6%). Off-target effects were absent in BCL11A-edited cells but observed at low frequencies in ZBTB7A/LRF-edited cells. Neither disruption significantly affected erythroid differentiation. These findings highlight the comparable contributions of ZBTB7A/LRF and BCL11A binding sites to γ-globin reactivation. CRISPR/Cas9 editing of either site may offer a potential therapeutic strategy for β<sup>0</sup>-thalassemia/HbE disease.