ArticleBlood2007
Locus control region elements HS1 and HS4 enhance the therapeutic efficacy of globin gene transfer in beta-thalassemic mice.
Article in Blood, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 51 citations in OpenAlex.
- Evaluation of Mono- and Bi-Functional GLOBE-Based Vectors for Therapy of β-Thalassemia byCells · 2023Article
- The Optimized γ-Globin Lentiviral Vector GGHI-mB-3D Leads to Nearly Therapeutic HbF Levels In Vitro in CD34Viruses · 2022Article
- Lentiviral globin gene therapy with reduced-intensity conditioning in adults with β-thalassemia: a phase 1 trial.Nature medicine · 2022Article
- 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
- Creating New β-Globin-Expressing Lentiviral Vectors by High-Resolution Mapping of Locus Control Region Enhancer Sequences.Molecular therapy. Methods & clinical development · 2020Article
- Improved Titer and Gene Transfer by Lentiviral Vectors Using Novel, Small β-Globin Locus Control Region Elements.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Targeted Integration and High-Level Transgene Expression in AAVS1 Transgenic Mice after In Vivo HSC Transduction with HDAd5/35++ Vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- High-level protein production in erythroid cells derived from in vivo transduced hematopoietic stem cells.Blood advances · 2019Article
- Phasor histone FLIM-FRET microscopy quantifies spatiotemporal rearrangement of chromatin architecture during the DNA damage response.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Gene Therapy For Beta-Thalassemia: Updated Perspectives.The application of clinical genetics · 2019Article
- Gene Therapy for Hemoglobinopathies.Human gene therapy · 2018Review
- An Optimized Lentiviral Vector Efficiently Corrects the Human Sickle Cell Disease Phenotype.Molecular therapy. Methods & clinical development · 2018Article
- Integrating HDAd5/35++ Vectors as a New Platform for HSC Gene Therapy of Hemoglobinopathies.Molecular therapy. Methods & clinical development · 2018Article
- Sickle cells produce functional immune modulators and cytotoxics.American journal of hematology · 2017Article
- Gene Addition Strategies for β-Thalassemia and Sickle Cell Anemia.Advances in experimental medicine and biology · 2017Review
- miRNA-embedded shRNAs for Lineage-specific BCL11A Knockdown and Hemoglobin F Induction.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- Gene therapy for hemoglobinopathies: the state of the field and the future.Hematology/oncology clinics of North America · 2014Review
- Article
- Complete TCR-α gene locus control region activity in T cells derived in vitro from embryonic stem cells.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
Globin gene transfer in autologous hematopoietic stem cells is a promising therapeutic option for subjects with beta-thalassemia major. In this approach, high level, erythroid-specific globin transgene expression should correct ineffective erythropoiesis and hemolytic anemia following the delivery of only 1 to 2 vector copies per cell. The generation of vectors that provide high-level globin expression and require low vector copy (VC) integration is therefore essential for both safety and efficacy. We show here the major roles played by 2 lesser-known locus control region elements, termed HS1 and HS4. Partial deletions within HS4 markedly reduce in vivo globin expression requiring multiple VC per cell to correct the anemia. Most strikingly, addition of HS1 to HS2-3-4 increases globin expression by 52%, yielding 9 g Hb/VC in beta-thalassemic mice. Thus, while vectors encoding HS2-3-4 provide curative levels of hemoglobin at 1 to 2 copies per cell, adding HS1 is a promising alternative strategy if upcoming clinical trials prove higher levels of expression to be necessary.
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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.