Enhanced γ-globin reactivation and sickle cell correction through a repressor-to-activator motif switch in the HBG1/2 promoters
Anne Chalumeau, Panagiotis Antoniou, Maria Bou Dames, Pierre Martinucci, Elena Retana, Pragya Gupta, Mike Firth, Muralidhar Reddivari, Aathira Sarath Chandran, Jonathan S. Yen, Martin Peterka, Marcello Maresca, Mégane Brusson, Annarita Miccio · 2026
Read Enhanced γ-globin reactivation and sickle cell correction through a repressor-to-activator motif switch in the HBG1/2 promoters by Anne Chalumeau, Panagiotis Antoniou, Maria Bou Dames, Pierre Martinucci, Elena Retana, Pragya Gupta, Mike Firth, Muralidhar Reddivari, Aathira Sarath Chandran, Jonathan S. Yen, Martin Peterka, Marcello Maresca, Mégane Brusson, Annarita Miccio (2026) in the Tower of Babel, a free online library of public-domain works preserved in clean, searchable text. No sign-up. The full text is served as a plain-text file at a predictable URL, where text is present: https://antarctic-labs.com/tower-of-babel/pmc-13330520.txt.
Description
Anne Chalumeau and team engineered a repressor-to-activator motif switch to reactivate fetal globin in sickle cell disease. Their 2026 study replaced the BCL11A repressor-binding site in fetal HBG1/2 promoters with a TAL1:GATA1 motif seen by transcriptional activators. Lasting fetal hemoglobin improves sickle cell disease, and transplant of autologous corrected blood stem cells offers promise, but promoter editing needed testing.
Prime editing nuclease installed the motif well in K562 cells, beating original prime editing, and blocking end-joining boosted editing. The strategy worked poorly in patient stem cells, so the team used CRISPR-Cas9 to disrupt the repressor site or install the new motif by homology-guided repair. Edited stem cells kept clonogenic capacity and became red blood cells with raised fetal globin expression and corrected sickling. The team presents the motif switch as a potent route to fetal globin reactivation.
Catalog record
| CREATOR | Anne Chalumeau, Panagiotis Antoniou, Maria Bou Dames, Pierre Martinucci, Elena Retana, Pragya Gupta, Mike Firth, Muralidhar Reddivari, Aathira Sarath Chandran, Jonathan S. Yen, Martin Peterka, Marcello Maresca, Mégane Brusson, Annarita Miccio |
|---|---|
| YEAR | 2026 |
| COLLECTION | PAPERS |
| FORMAT | TXT |
| FILE SIZE | 91 KB |
| VERSION | 1.0 |
| LICENSE | CC BY 4.0 |
| RIGHTS | CC BY |
| SOURCE | Europe PMC |