ArticleThe Journal of clinical investigation2004
High-level beta-globin expression and preferred intragenic integration after lentiviral transduction of human cord blood stem cells.
Article in The Journal of clinical investigation, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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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
44 citing papers in PubMed, 113 citations in OpenAlex.
- Long-term outcomes of lentiviral gene therapy for the β-hemoglobinopathies: the HGB-205 trial.Nature medicine · 2022Trial
- The Molecular Pathology of Non-Malignant Haematological Disease.British journal of biomedical science · 2026Review
- Receptor Tyrosine Kinase Profiling Identifies Chronic Constitutive Floodgate Oxidative Signaling in Glutathione-Independent Human Mammary Luminal Progenitor Cells.bioRxiv : the preprint server for biology · 2025Article
- Evolution of Gene Therapy, Historical Perspective.Hematology/oncology clinics of North America · 2022Review
- Review
- The Future of Gene Therapy for Transfusion-Dependent Beta-Thalassemia: The Power of the Lentiviral Vector for Genetically Modified Hematopoietic Stem Cells.Frontiers in pharmacology · 2021Review
- Enhanced Transduction of Human Hematopoietic Stem Cells by AAV6 Vectors: Implications in Gene Therapy and Genome Editing.Molecular therapy. Nucleic acids · 2020Article
- Isolation and characterization of a new basal-like luminal progenitor in human breast tissue.Stem cell research & therapy · 2019Article
- VENTX induces expansion of primitive erythroid cells and contributes to the development of acute myeloid leukemia in mice.Oncotarget · 2016Article
- A New Approach in Gene Therapy of Glioblastoma Multiforme: Human Olfactory Ensheathing Cells as a Novel Carrier for Suicide Gene Delivery.Molecular neurobiology · 2016Article
- Gene Therapy for Hemoglobinopathies: Tremendous Successes and Remaining Caveats.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Current and future alternative therapies for beta-thalassemia major.Biomedical journal · 2016Review
- Gene Therapy of the β-Hemoglobinopathies by Lentiviral Transfer of the β(A(T87Q))-Globin Gene.Human gene therapy · 2016Article
- Gene therapy for hemoglobin disorders - a mini-review.Journal of rare diseases research & treatment · 2016Article
- Characterization of Epithelial Progenitors in Normal Human Palatine Tonsils and Their HPV16 E6/E7-Induced Perturbation.Stem cell reports · 2015Article
- Disruption of IKAROS activity in primitive chronic-phase CML cells mimics myeloid disease progression.Blood · 2015Article
- Recent trends in the gene therapy of β-thalassemia.Journal of blood medicine · 2015Review
- A dominant-negative isoform of IKAROS expands primitive normal human hematopoietic cells.Stem cell reports · 2014Article
- The Lin28b-let-7-Hmga2 axis determines the higher self-renewal potential of fetal haematopoietic stem cells.Nature cell biology · 2013Article
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10 authors at 4 institutions in 2 countries.
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Abstract
Transplantation of genetically corrected autologous hematopoietic stem cells is an attractive approach for the cure of sickle-cell disease and beta-thalassemia. Here, we infected human cord blood cells with a self-inactivating lentiviral vector encoding an anti-sickling betaA-T87Q-globin transgene and analyzed the transduced progeny produced over a 6-month period after transplantation of the infected cells directly into sublethally irradiated NOD/LtSz-scid/scid mice. Approximately half of the human erythroid and myeloid progenitors regenerated in the mice containing the transgene, and erythroid cells derived in vitro from these in vivo-regenerated cells produced high levels of betaA-T87Q-globin protein. Linker-mediated PCR analysis identified multiple transgene-positive clones in all mice analyzed with 2.1 +/- 0.1 integrated proviral copies per cell. Genomic sequencing of vector-containing fragments showed that 86% of the proviral inserts had occurred within genes, including several genes implicated in human leukemia. These findings indicate effective transduction of very primitive human cord blood cells with a candidate therapeutic lentiviral vector resulting in the long-term and robust, erythroid-specific production of therapeutically relevant levels of beta-globin protein. However, the frequency of proviral integration within genes that regulate hematopoiesis points to a need for additional safety modifications.
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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.