Molecular Therapy — Nucleic Acids· 2026Q1
Beyond repressor disruption: Designing activator motifs to boost fetal hemoglobin
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- Q1SCImago
- 2026year
Short summary
Researchers replaced a repressor binding site in fetal hemoglobin promoters with an activator motif, leading to robust γ-globin expression and reduced sickling in sickle cell disease cells.
AI-generated from the title and abstract; the full text is not read.
Key points
- Novel strategy replaces repressor binding site with an activator motif in fetal hemoglobin promoters.
- Engineered promoters (HBG1/2) support robust γ-globin expression.
- Reduced sickling observed in erythroid cells from SCD HSPCs.
- Approach moves beyond simple repressor disruption for HbF reactivation.
AI-generated from the title and abstract; the full text is not read.
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).
The authors' abstract, as published at the source. Molecular Therapy — Nucleic Acids, 2026 · DOI ↗
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Field: Genetics (Medicine)
GeneticsMedicine