ArticleBlood2016
Forced chromatin looping raises fetal hemoglobin in adult sickle cells to higher levels than pharmacologic inducers.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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.
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Who cites it
45 citing papers in PubMed, 81 citations in OpenAlex.
- Cohesin mutations and chromatin changes in cancer.International journal of cancer · 2026Review
- Single-stranded DNA-binding proteins are essential components of the architectural LDB1 protein complex.Molecular cell · 2025Article
- DNA regulatory element cooperation and competition in transcription.BMB reports · 2024Review
- Gene-environmental influence of space and microgravity on red blood cells with sickle cell disease.NPJ genomic medicine · 2024Review
- YY1-controlled regulatory connectivity and transcription are influenced by the cell cycle.Nature genetics · 2024Article
- In vivo hematopoietic stem cell modification by mRNA delivery.Science (New York, N.Y.) · 2023Article
- Enhancer Function in the 3D Genome.Genes · 2023Review
- Novel lentiviral vectors for gene therapy of sickle cell disease combining gene addition and gene silencing strategies.Molecular therapy. Nucleic acids · 2023Article
- Identification of a genomic DNA sequence that quantitatively modulates KLF1 transcription factor expression in differentiating human hematopoietic cells.Scientific reports · 2023Article
- Forced enhancer-promoter rewiring to alter gene expression in animal models.Molecular therapy. Nucleic acids · 2023Article
- PUM1 mediates the posttranscriptional regulation of human fetal hemoglobin.Blood advances · 2022Article
- Targeting Genetic Modifiers of HBG Gene Expression in Sickle Cell Disease: The miRNA Option.Molecular diagnosis & therapy · 2022Review
- Pharmacological Induction of Fetal Hemoglobin in β-Thalassemia and Sickle Cell Disease: An Updated Perspective.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Article
- Sickle cell disease: progress towards combination drug therapy.British journal of haematology · 2021Review
- Engineering 3D genome organization.Nature reviews. Genetics · 2021Review
- Lentiviral vector ALS20 yields high hemoglobin levels with low genomic integrations for treatment of beta-globinopathies.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Manipulation of Developmental Gamma-Globin Gene Expression: an Approach for Healing Hemoglobinopathies.Molecular and cellular biology · 2020Review
- Fetal hemoglobin in sickle cell anemia.Blood · 2020Review
- Modulating gene regulation to treat genetic disorders.Nature reviews. Drug discovery · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Overcoming the silencing of the fetal γ-globin gene has been a long-standing goal in the treatment of sickle cell disease (SCD). The major transcriptional enhancer of the β-globin locus, called the locus control region (LCR), dynamically interacts with the developmental stage-appropriate β-type globin genes via chromatin looping, a process requiring the protein Ldb1. In adult erythroid cells, the LCR can be redirected from the adult β- to the fetal γ-globin promoter by tethering Ldb1 to the human γ-globin promoter with custom-designed zinc finger (ZF) proteins (ZF-Ldb1), leading to reactivation of γ-globin gene expression. To compare this approach to pharmacologic reactivation of fetal hemoglobin (HbF), hematopoietic cells from patients with SCD were treated with a lentivirus expressing the ZF-Ldb1 or with chemical HbF inducers. The HbF increase in cells treated with ZF-Ldb1 was more than double that observed with decitabine and pomalidomide; butyrate had an intermediate effect whereas tranylcypromine and hydroxyurea showed relatively low HbF reactivation. ZF-Ldb1 showed comparatively little toxicity, and reduced sickle hemoglobin (HbS) synthesis as well as sickling of SCD erythroid cells under hypoxic conditions. The efficacy and low cytotoxicity of lentiviral-mediated ZF-Ldb1 gene transfer compared with the drug regimens support its therapeutic potential for the treatment of SCD.
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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.