Work

Beyond repressor disruption: Designing activator motifs to boost fetal hemoglobin

Year: 2026

Type: article

Abstract: Fetal hemoglobin (HbF) reactivation is now a powerful and clinically validated strategy for sickle cell disease (SCD). Many genome-editing approaches achieve this by disrupting regulatory sequences involved in γ-globin silencing, such as the BCL11A erythroid enhancer. In a recent issue of Molecular Therapy Nucleic Acids, Chalumeau et al.1 replaced the BCL11A binding site in the HBG1/2 promoters with a composite TAL1:GATA1 activating motif rather than only disrupting a repressor site. The edited promoters supported robust γ-globin expression and reduced sickling in erythroid cells derived from SCD hematopoietic stem and progenitor cells (HSPCs).

Source: Molecular Therapy — Nucleic Acids

DOI: 10.1016/j.omtn.2026.103147

Author: Selami Demirci

Institutions: National Institutes of Health, National Heart, Lung, and Blood Institute

Language: English

Topic: Hemoglobinopathies and Related Disorders

Subfield: Genetics (clinical)

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,900