ArticleBlood advances2019
Genome editing of HBG1 and HBG2 to induce fetal hemoglobin.
Article in Blood advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
117 citing papers in PubMed, 2 syntheses or guidelines pooled it, 175 citations in OpenAlex.
- Using Clustered Regularly Interspaced Short Palindromic Repeats gene editing to induce permanent expression of fetal hemoglobin in β-thalassemia and sickle cell disease: A comparative meta-analysis.Frontiers in medicine · 2022Pooled it
- Persistence of CRISPR/Cas9 gene edited hematopoietic stem cells following transplantation: A systematic review and meta-analysis of preclinical studies.Stem cells translational medicine · 2021Pooled it
- Zinc finger nuclease-mediated gene editing in hematopoietic stem cells results in reactivation of fetal hemoglobin in sickle cell disease.Scientific reports · 2024Trial
- CRISPR-Cas9 Editing of theThe New England journal of medicine · 2023Trial
- CRISPR-HAWK: haplotype- and variant-aware guide design toolkit for CRISPR-Cas.Bioinformatics (Oxford, England) · 2026Article
- Enhanced γ-globin reactivation and sickle cell correction through a repressor-to-activator motif switch in theMolecular therapy. Nucleic acids · 2026Article
- The Journey of Gene Therapy in Sickle Cell Disease: How Molecular Advances Meet Clinical Care.Cells · 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
- Investigating the Efficacy of the CRISPR/Cas9 Gene-Editing System for Targeting the HBB FSC 36-37 (-T) Mutation Locus in Hematopoietic Stem Cells.Molecular biotechnology · 2026Article
- Monitoring biological effects of somatic cell genome editing.Nature reviews. Genetics · 2026Review
- Complex HBB gene editing outcomes revealed by a fluorescent reporter cell model.Molecular therapy. Nucleic acids · 2026Article
- In vivo genome editing of human haematopoietic stem cells for treatment of blood disorders using mRNA delivery.Nature biomedical engineering · 2026Article
- Microfluidic capillary transit velocity as a functional measure for sickle cell disease andLab on a chip · 2026Article
- Functional correction and genome integrity with duplex base editing of β-thalassemic hematopoietic stem cells.Genome biology · 2026Article
- CRISPR-HAWK: Haplotype- and Variant-aware guide design toolkit for CRISPR-Cas.bioRxiv : the preprint server for biology · 2025Article
- CRISPR editing of HPFH3 genotype induces γ-globin expression and reverses sickle cell disease and β-thalassemia phenotypes.Stem cell research & therapy · 2025Article
- Gene Therapy of Beta Hemoglobinopathies.Biomedicines · 2025Review
- Progress and prospect of minicircle as a minimized non-viral DNA vector in gene therapy and regenerative medicine.Molecular therapy. Nucleic acids · 2025Review
- Pleiotropic Effects of Polymorphisms in theInternational journal of molecular sciences · 2025Article
- Multiplex base editing of BCL11A regulatory elements to treat sickle cell disease.Cell reports. Medicine · 2025Article
57 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 6 institutions in 2 countries.
Funding
Abstract
Induction of fetal hemoglobin (HbF) via clustered regularly interspaced short palindromic repeats/Cas9-mediated disruption of DNA regulatory elements that repress γ-globin gene (HBG1 and HBG2) expression is a promising therapeutic strategy for sickle cell disease (SCD) and β-thalassemia, although the optimal technical approaches and limiting toxicities are not yet fully defined. We disrupted an HBG1/HBG2 gene promoter motif that is bound by the transcriptional repressor BCL11A. Electroporation of Cas9 single guide RNA ribonucleoprotein complex into normal and SCD donor CD34+ hematopoietic stem and progenitor cells resulted in high frequencies of on-target mutations and the induction of HbF to potentially therapeutic levels in erythroid progeny generated in vitro and in vivo after transplantation of hematopoietic stem and progenitor cells into nonobese diabetic/severe combined immunodeficiency/Il2rγ-/-/KitW41/W41 immunodeficient mice. On-target editing did not impair CD34+ cell regeneration or differentiation into erythroid, T, B, or myeloid cell lineages at 16 to 17 weeks after xenotransplantation. No off-target mutations were detected by targeted sequencing of candidate sites identified by circularization for in vitro reporting of cleavage effects by sequencing (CIRCLE-seq), an in vitro genome-scale method for detecting Cas9 activity. Engineered Cas9 containing 3 nuclear localization sequences edited human hematopoietic stem and progenitor cells more efficiently and consistently than conventional Cas9 with 2 nuclear localization sequences. Our studies provide novel and essential preclinical evidence supporting the safety, feasibility, and efficacy of a mechanism-based approach to induce HbF for treating hemoglobinopathies.
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Registered trials
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.