ArticleScience (New York, N.Y.)2018
Domain-focused CRISPR screen identifies HRI as a fetal hemoglobin regulator in human erythroid cells.
Article in Science (New York, N.Y.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers.
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Who cites it
98 citing papers in PubMed, 147 citations in OpenAlex.
- Regulatory mechanism of heme-regulated inhibitor through autophosphorylation-driven activation and heme-induced deactivation.Journal of biochemistry · 2026Article
- Article
- New Gene Therapy Strategy for β-Thalassemia.Stem cell reviews and reports · 2026Review
- A Comprehensive Review on CRISPR-Based Screening and Its Applications.Molecular biotechnology · 2026Review
- Article
- Dissecting polycomb complexes for enhanced fetal hemoglobin production.bioRxiv : the preprint server for biology · 2026Article
- Inducible, split base editors for in vivo cancer functional genomics.Nature biotechnology · 2026Article
- CRISPR-based functional genomics for dissecting therapeutic dependency in primary acute myeloid leukemia samples.Molecular cell · 2026Article
- Highly discriminative globin gene activation by the noncanonical BAF chromatin remodeling complex.Blood · 2026Article
- Learning genetic perturbation effects with variational causal inference.PLoS computational biology · 2026Article
- Discovery of a Novel DNMT1 Inhibitor with Improved Efficacy in Treating β-Thalassemia.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Lineage-determining transcription factors constrain cohesin to drive multi-enhancer oncogene regulation.Nature cell biology · 2026Article
- Mechanisms of Globin Gene Regulation in Mammals.Annual review of genetics · 2025Review
- Learning Genetic Perturbation Effects with Variational Causal Inference.bioRxiv : the preprint server for biology · 2025Article
- Advancements in CRISPR/Cas systems for disease treatment.Acta pharmaceutica Sinica. B · 2025Review
- A one-base therapeutic insertion in the HBG2 distal promoter reactivates γ-globin expression.Experimental hematology & oncology · 2025Article
- Wingless strain created using binary transgenic CRISPR/Cas9 alleviates concerns about mass rearing of Hermetia illucens.Communications biology · 2024Article
- Transcriptional regulators of fetal hemoglobin.Hematology, transfusion and cell therapy · 2024Review
- Review
- Prevalence of and gene regulatory constraints on transcriptional adaptation in single cells.Genome biology · 2024Article
38 more citing papers are in PubMed but not listed here.
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
Abstract
Increasing fetal hemoglobin (HbF) levels in adult red blood cells provides clinical benefit to patients with sickle cell disease and some forms of β-thalassemia. To identify potentially druggable HbF regulators in adult human erythroid cells, we employed a protein kinase domain-focused CRISPR-Cas9-based genetic screen with a newly optimized single-guide RNA scaffold. The screen uncovered the heme-regulated inhibitor HRI (also known as EIF2AK1), an erythroid-specific kinase that controls protein translation, as an HbF repressor. HRI depletion markedly increased HbF production in a specific manner and reduced sickling in cultured erythroid cells. Diminished expression of the HbF repressor BCL11A accounted in large part for the effects of HRI depletion. Taken together, these results suggest HRI as a potential therapeutic target for hemoglobinopathies.
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Registered trials
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