ArticleBlood advances2021
Correction of β-thalassemia by CRISPR/Cas9 editing of the α-globin locus in human hematopoietic stem cells.
Article in Blood advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 75 citations in OpenAlex.
- MN•CS•IO System: Cross-Species Study for HBB Function in High-Altitude Hypoxia Adaptation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Synergistic cooperation between progranulin and Jak2/Stat3 signaling determines definitive myeloid cell fate.Cell reports · 2026Article
- Illuminating "the dark side of the HBB": Visualizing the full spectrum of Cas9 outcomes.Molecular therapy. Nucleic acids · 2026Article
- Complex HBB gene editing outcomes revealed by a fluorescent reporter cell model.Molecular therapy. Nucleic acids · 2026Article
- Investigate the Effect of ZFP64 on mRNA Expression of HBG Based on Bioinformatics and Experimental Validation.Cell biochemistry and biophysics · 2025Article
- Article
- 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
- Targeted gene editing and near-universal cDNA insertion of CYBA and CYBB as a treatment for chronic granulomatous disease.Nature communications · 2025Article
- Beyond transfusions and transplants: genomic innovations rewriting the narrative of thalassemia.Annals of hematology · 2025Review
- The epigenetic revolution in hematology: from benchside breakthroughs to clinical transformations.Clinical and experimental medicine · 2025Review
- Biosafety considerations triggered by genome-editing technologies.Biosafety and health · 2025Review
- Simultaneous Co-transplantation for Highly Efficient Cell Therapy.Current stem cell research & therapy · 2025Review
- Harnessing CRISPR potential for intervertebral disc regeneration strategies.Frontiers in bioengineering and biotechnology · 2025Review
- Advances in Nanoparticles as Non-Viral Vectors for Efficient Delivery of CRISPR/Cas9.Pharmaceutics · 2024Review
- CRISPR technology in human diseases.MedComm · 2024Review
- CRISPR-Cas9 system: a novel and promising era of genotherapy for beta-hemoglobinopathies, hematological malignancy, and hemophilia.Annals of hematology · 2024Review
- Review
- Review
- Interplay between α-thalassemia and β-hemoglobinopathies: Translating genotype-phenotype relationships into therapies.HemaSphere · 2024Article
- A simultaneous knockout knockin genome editing strategy in HSPCs potently inhibits CCR5- and CXCR4-tropic HIV-1 infection.Cell stem cell · 2024Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
β-thalassemias (β-thal) are a group of blood disorders caused by mutations in the β-globin gene (HBB) cluster. β-globin associates with α-globin to form adult hemoglobin (HbA, α2β2), the main oxygen-carrier in erythrocytes. When β-globin chains are absent or limiting, free α-globins precipitate and damage cell membranes, causing hemolysis and ineffective erythropoiesis. Clinical data show that severity of β-thal correlates with the number of inherited α-globin genes (HBA1 and HBA2), with α-globin gene deletions having a beneficial effect for patients. Here, we describe a novel strategy to treat β-thal based on genome editing of the α-globin locus in human hematopoietic stem/progenitor cells (HSPCs). Using CRISPR/Cas9, we combined 2 therapeutic approaches: (1) α-globin downregulation, by deleting the HBA2 gene to recreate an α-thalassemia trait, and (2) β-globin expression, by targeted integration of a β-globin transgene downstream the HBA2 promoter. First, we optimized the CRISPR/Cas9 strategy and corrected the pathological phenotype in a cellular model of β-thalassemia (human erythroid progenitor cell [HUDEP-2] β0). Then, we edited healthy donor HSPCs and demonstrated that they maintained long-term repopulation capacity and multipotency in xenotransplanted mice. To assess the clinical potential of this approach, we next edited β-thal HSPCs and achieved correction of α/β globin imbalance in HSPC-derived erythroblasts. As a safer option for clinical translation, we performed editing in HSPCs using Cas9 nickase showing precise editing with no InDels. Overall, we described an innovative CRISPR/Cas9 approach to improve α/β globin imbalance in thalassemic HSPCs, paving the way for novel therapeutic strategies for β-thal.
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