ArticleThe EMBO journal1994
Mutagenesis of retroviral vectors transducing human beta-globin gene and beta-globin locus control region derivatives results in stable transmission of an active transcriptional structure.
Article in The EMBO journal, 1994. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 160 citations in OpenAlex.
- Gene Therapy for β-Haemoglobinopathies: From Molecular Correction to Curative Medicine.Biomedicines · 2026Review
- Evaluation of Mono- and Bi-Functional GLOBE-Based Vectors for Therapy of β-Thalassemia byCells · 2023Article
- 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
- 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
- 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
- Gene Therapy for β-Hemoglobinopathies.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Review
- Gene Addition Strategies for β-Thalassemia and Sickle Cell Anemia.Advances in experimental medicine and biology · 2017Review
- The potential of gene therapy approaches for the treatment of hemoglobinopathies: achievements and challenges.Therapeutic advances in hematology · 2016Review
- Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease.Blood · 2016Review
- 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: progress and predictions.Proceedings. Biological sciences · 2015Review
- Long-term and efficient expression of human β-globin gene in a hematopoietic cell line using a new site-specific integrating non-viral system.Gene therapy · 2015Article
- Gene therapy for hemoglobinopathies: the state of the field and the future.Hematology/oncology clinics of North America · 2014Review
- Development of gene therapy for thalassemia.Cold Spring Harbor perspectives in medicine · 2012Review
- Recent advances in gene therapy for thalassemia.Journal of pharmacy & bioallied sciences · 2012Article
- Cotransduction with MGMT and Ubiquitous or Erythroid-Specific GFP Lentiviruses Allows Enrichment of Dual-Positive Hematopoietic Progenitor Cells In Vivo.ISRN hematology · 2012Article
- Review
- The Ongoing Challenge of Hematopoietic Stem Cell-Based Gene Therapy for β-Thalassemia.Stem cells international · 2011Article
- Gene therapy in thalassemia and hemoglobinopathies.Mediterranean journal of hematology and infectious diseases · 2009Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Retrovirus-mediated gene transfer of the human beta-globin gene into hematopoietic stem cells is an attractive approach to the therapy of human beta-globin gene disorders. However, expression of the transduced beta-globin gene linked to its proximal cis-acting sequences (-0.8 to +0.3 kb from the cap site) is considerably below the level required for a significant therapeutic effect. The discovery of the beta-locus control region (beta-LCR), organized in four major DNase I hypersensitive sites far upstream of the human beta-like globin gene cluster, provided a potential means to achieve a high level of expression of a linked human beta-globin gene, but initial attempts to incorporate beta-LCR derivatives in retroviral vectors resulted in the production of low-titer viruses with multiple rearrangements of the transmitted proviral structures. We now describe how extensive mutagenesis of the transduced beta-globin gene, eliminating a 372 bp intronic segment and multiple reverse polyadenylation and splicing signals, increases viral titer significantly and restores stability of proviral transmission upon infection of cell lines and bone marrow-repopulating cells. These optimized vectors have enabled us to analyze the expression properties of various retrovirally transduced beta-LCR derivatives in dimethylsulfoxide-induced murine erythroleukemia cells and to achieve ratios of human beta-globin/murine beta maj-globin mRNA, on a per gene basis, as high as 80%.
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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.