ArticleBlood2021
Enhanced HbF reactivation by multiplex mutagenesis of thalassemic CD34+ cells in vitro and in vivo.
Article in Blood, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 40 citations in OpenAlex.
- Electroporation for High-Efficiency Delivery of CRISPR to Hematopoietic Cells.Methods in molecular biology (Clifton, N.J.) · 2027Article
- New Gene Therapy Strategy for β-Thalassemia.Stem cell reviews and reports · 2026Review
- Engraftment Outcome of CRISPR/Cas9-Edited Hematopoietic Stem Cells for Genetic Diseases: A Systematic Review and Meta-Analysis of Preclinical Evidence.Journal of hematology · 2026Article
- Functional correction and genome integrity with duplex base editing of β-thalassemic hematopoietic stem cells.Genome biology · 2026Article
- Comparative analysis of CRISPR-Cas9, lentiviral transduction, and base editing for sickle cell disease in a murine model.Blood advances · 2026Article
- Disrupting ZBTB7A or BCL11A binding sites reactivates fetal hemoglobin in erythroblasts from healthy and βScientific reports · 2025Article
- A common TBP-binding site mutation elevates fetal hemoglobin levels by competitive globin switching change in β-thalassemia.Blood advances · 2025Article
- Epigenetic Regulation of Erythropoiesis: From Developmental Programs to Therapeutic Targets.International journal of molecular sciences · 2025Review
- Article
- Advancements in CRISPR/Cas systems for disease treatment.Acta pharmaceutica Sinica. B · 2025Review
- Large-scale discovery of potent, compact and erythroid specific enhancers for gene therapy vectors.Nature communications · 2025Article
- Current and future treatments for sickle cell disease: From hematopoietic stem cell transplantation to in vivo gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Detection of CRISPR/Cas9-Mediated Fetal Hemoglobin Reactivation in Erythroblasts Derived from Cord Blood-Hematopoietic Stem Cells.Molecular biotechnology · 2025Article
- A one-base therapeutic insertion in the HBG2 distal promoter reactivates γ-globin expression.Experimental hematology & oncology · 2025Article
- Expanding Horizons of CRISPR/Cas Technology: Clinical Advancements, Therapeutic Applications, and Challenges in Gene Therapy.International journal of molecular sciences · 2024Review
- Article
- Bone-marrow-homing lipid nanoparticles for genome editing in diseased and malignant haematopoietic stem cells.Nature nanotechnology · 2024Article
- CRISPR technology in human diseases.MedComm · 2024Review
- Non-viral DNA delivery and TALEN editing correct the sickle cell mutation in hematopoietic stem cells.Nature communications · 2024Article
- An Optimized Human Erythroblast Differentiation System Reveals Cholesterol-Dependency of Robust Production of Cultured Red Blood Cells Ex Vivo.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
Thalassemia or sickle cell patients with hereditary persistence of fetal hemoglobin (HbF) have an ameliorated clinical phenotype and, in some cases, can achieve transfusion independence. Inactivation via genome editing of γ-globin developmental suppressors, such as BCL11A or LRF/ZBTB7A, or of their binding sites, have been shown to significantly increase expression of endogenous HbF. To broaden the therapeutic window beyond a single-editing approach, we have explored combinations of cis- and trans-editing targets to enhance HbF reactivation. Multiplex mutagenesis in adult CD34+ cells was well tolerated and did not lead to any detectable defect in the cells' proliferation and differentiation, either in vitro or in vivo. The combination of 1 trans and 1 cis mutation resulted in high editing retention in vivo, coupled with almost pancellular HbF expression in NBSGW mice. The greater in vivo performance of this combination was also recapitulated using a novel helper-dependent adenoviral-CRISPR vector (HD-Ad-dualCRISPR) in CD34+ cells from β-thalassemia patients transplanted to NBSGW mice. A pronounced increase in HbF expression was observed in human red blood cells in mice with established predominant β0/β0-thalassemic hemopoiesis after in vivo injection of the HD-Ad-dualCRISPR vector. Collectively, our data suggest that the combination of cis and trans fetal globin reactivation mutations has the potential to significantly increase HbF both totally and on a per cell basis over single editing and could thus provide significant clinical benefit to patients with severe β-globin phenotype.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.