ArticleNature communications2022
Base-editing-mediated dissection of a γ-globin cis-regulatory element for the therapeutic reactivation of fetal hemoglobin expression.
Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 69 citations in OpenAlex.
- Electroporation for High-Efficiency Delivery of CRISPR to Hematopoietic Cells.Methods in molecular biology (Clifton, N.J.) · 2027Article
- Article
- Base editing for precision therapeutics.Cell genomics · 2026Review
- Enhanced γ-globin reactivation and sickle cell correction through a repressor-to-activator motif switch in theMolecular therapy. Nucleic acids · 2026Article
- Gene editing of hematopoietic stem cells: applications and advances.International journal of hematology · 2026Review
- New Gene Therapy Strategy for β-Thalassemia.Stem cell reviews and reports · 2026Review
- Gene Therapy for β-Haemoglobinopathies: From Molecular Correction to Curative Medicine.Biomedicines · 2026Review
- Molecular and therapeutic frontiers in anemia therapy.The Journal of clinical investigation · 2026Review
- Functional correction and genome integrity with duplex base editing of β-thalassemic hematopoietic stem cells.Genome biology · 2026Article
- Single-strand deaminase-assisted editing for functional RNA manipulation.Nature biotechnology · 2026Article
- Gene therapy for hemoglobinopathies: Clinical trial results and biology of hematopoietic stem cell and the bone marrow niche.Cell reports. Medicine · 2025Review
- MAZ regulates fetal hemoglobin repression by activating MYB transcription.Scientific reports · 2025Article
- CRISPR-based therapeutic genome editing for inherited blood disorders.Nature reviews. Drug discovery · 2025Review
- Article
- Multiplex base editing of BCL11A regulatory elements to treat sickle cell disease.Cell reports. Medicine · 2025Article
- Emerging Therapies for Sickle Cell Disease: From Symptom Management to Curative Gene Therapy.Cureus · 2025Review
- Genetic Engineering in Hematopoietic Stem Cells for β-Hemoglobinopathies Treatment: Advances, Challenges, and Clinical Translation.International journal of hematology-oncology and stem cell research · 2025Review
- Engraftment and persistence ofScience translational medicine · 2025Article
- Beyond transfusions and transplants: genomic innovations rewriting the narrative of thalassemia.Annals of hematology · 2025Review
- Disrupting ZBTB7A or BCL11A binding sites reactivates fetal hemoglobin in erythroblasts from healthy and βScientific reports · 2025Article
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Authors and funding
23 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sickle cell disease and β-thalassemia affect the production of the adult β-hemoglobin chain. The clinical severity is lessened by mutations that cause fetal γ-globin expression in adult life (i.e., the hereditary persistence of fetal hemoglobin). Mutations clustering ~200 nucleotides upstream of the HBG transcriptional start sites either reduce binding of the LRF repressor or recruit the KLF1 activator. Here, we use base editing to generate a variety of mutations in the -200 region of the HBG promoters, including potent combinations of four to eight γ-globin-inducing mutations. Editing of patient hematopoietic stem/progenitor cells is safe, leads to fetal hemoglobin reactivation and rescues the pathological phenotype. Creation of a KLF1 activator binding site is the most potent strategy - even in long-term repopulating hematopoietic stem/progenitor cells. Compared with a Cas9-nuclease approach, base editing avoids the generation of insertions, deletions and large genomic rearrangements and results in higher γ-globin levels. Our results demonstrate that base editing of HBG promoters is a safe, universal strategy for treating β-hemoglobinopathies.
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