ArticleProceedings of the National Academy of Sciences of the United States of America2008
In vivo selection of genetically modified erythroblastic progenitors leads to long-term correction of beta-thalassemia.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02453477 (A Phase I/II Study Evaluating Safety and Efficacy of Autologous Hematopoietic Stem Cells Genetically Modified With GLOBE Lentiviral Vector Encoding for the Human Beta-globin Gene for the Treatment of Patients Affected by Transfusion Dependent Beta-thalassemia), which is not on this map. Cited by 88 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.
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.
A Phase I/II Study Evaluating Safety and Efficacy of Autologous Hematopoietic Stem Cells Genetically Modified With GLOBE Lentiviral Vector Encoding for the Human Beta-globin Gene for the Treatment of Patients Affected by Transfusion Dependent Beta-thalassemia
Who cites it
88 citing papers in PubMed, 149 citations in OpenAlex.
- Clinical outcomes of lentiviral vector gene therapy for sickle cell disease.Blood advances · 2026Trial
- Severe inflammation and lineage skewing are associated with poor engraftment of engineered hematopoietic stem cells in patients with sickle cell disease.Nature communications · 2025Trial
- Intrabone hematopoietic stem cell gene therapy for adult and pediatric patients affected by transfusion-dependent ß-thalassemia.Nature medicine · 2019Trial
- Lentiviral vectors for hematopoietic stem cell gene therapy restore α-globin expression in α-thalassemia red blood cells.Cell reports. Medicine · 2025Article
- Gene therapy for sickle cell disease: recent advances, clinical trials and future directions.Cytotherapy · 2025Review
- Epigenetic Regulation of Erythropoiesis: From Developmental Programs to Therapeutic Targets.International journal of molecular sciences · 2025Review
- Ex vivo modification of hematopoietic stem and progenitor cells for gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- An erythroid-specific lentiviral vector improves anemia and iron metabolism in a new model of XLSA.Blood · 2025Article
- Therapeutic gene correction of HBB frameshift CD41-42 (-TCTT) deletion in human hematopoietic stem cells.Advanced biotechnology · 2025Article
- Evaluation of Mono- and Bi-Functional GLOBE-Based Vectors for Therapy of β-Thalassemia byCells · 2023Article
- In vivo hematopoietic stem cell modification by mRNA delivery.Science (New York, N.Y.) · 2023Article
- Precision Editing as a Therapeutic Approach for β-Hemoglobinopathies.International journal of molecular sciences · 2023Review
- Review
- Review
- Combination of lentiviral and genome editing technologies for the treatment of sickle cell disease.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Recent advances in lentiviral vectors for gene therapy.Science China. Life sciences · 2021Review
- Coordinated β-globin expression and α2-globin reduction in a multiplex lentiviral gene therapy vector for β-thalassemia.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Genome-based therapeutic interventions for β-type hemoglobinopathies.Human genomics · 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
- Correction of β-thalassemia by CRISPR/Cas9 editing of the α-globin locus in human hematopoietic stem cells.Blood advances · 2021Article
28 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
10 authors at 5 institutions in 2 countries.
Funding
Abstract
Gene therapy for beta-thalassemia requires stable transfer of a beta-globin gene into hematopoietic stem cells (HSCs) and high and regulated hemoglobin expression in the erythroblastic progeny. We developed an erythroid-specific lentiviral vector driving the expression of the human beta-globin gene from a minimal promoter/enhancer element containing two hypersensitive sites from the beta-globin locus control region. Transplantation of transduced HSCs into thalassemic mice leads to stable and long-term correction of anemia with all red blood cells expressing the transgene. A frequency of 30-50% of transduced HSCs, harboring an average vector copy number per cell of 1, was sufficient to fully correct the thalassemic phenotype. In the mouse model of Cooley's anemia transplantation of transduced cells rescues lethality, leading to either a normal or a thalassemia intermedia phenotype. We show that genetically corrected erythroblasts undergo in vivo selection with preferential survival of progenitors harboring proviral integrations in genome sites more favorable to high levels of vector-derived expression. These data provide a rationale for a gene therapy approach to beta-thalassemia based on partially myeloablative transplantation protocols.
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What OpenQuestion holds
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.