ArticleGene therapy2005
Use of the hereditary persistence of fetal hemoglobin 2 enhancer to increase the expression of oncoretrovirus vectors for human gamma-globin.
Article in Gene therapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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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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.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- The Optimized γ-Globin Lentiviral Vector GGHI-mB-3D Leads to Nearly Therapeutic HbF Levels In Vitro in CD34Viruses · 2022Article
- 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
- Gene therapy for hemoglobinopathies: progress and challenges.Translational research : the journal of laboratory and clinical medicine · 2013Review
- 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
- The new self-inactivating lentiviral vector for thalassemia gene therapy combining two HPFH activating elements corrects human thalassemic hematopoietic stem cells.Human gene therapy · 2012Article
- 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
- Beta-globin LCR and intron elements cooperate and direct spatial reorganization for gene therapy.PLoS genetics · 2008Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
The development of oncoretrovirus vectors for human gamma-globin has been hampered by problems of low expression and gene silencing. In order to address these problems, we investigated an enhancer element identified from individuals with deletional hereditary persistence of fetal hemoglobin 2 (HPFH2), a genetic condition characterized by elevated levels of gamma-globin in adults. Plasmid transfection studies in erythroid MEL (murine erythroleukemia) cells demonstrated the HPFH2 element could function synergistically with the beta-globin locus control region to enhance the expression of an Agamma-globin gene with a truncated -382 bp promoter. A series of oncoretrovirus vectors were subsequently generated that contain an expression cassette for Agamma-globin linked to various combinations of the HPFH2 enhancer, the alpha-globin HS40 enhancer, and several versions of the promoter from Agamma-globin or beta-globin. Expression analysis in transduced MEL cell clones revealed very high levels of promoter-autonomous silencing that was at least partially abrogated by the HPFH2 enhancer. The vector containing a combination of a -201 bp Agamma-globin gene promoter with the Greek HPFH -117 point mutation and both the HPFH2 and HS40 enhancers exhibited no signs of vector silencing and was expressed at 248+/-99% per copy of mouse alpha-globin (62% of total alpha-globin). This represents a significant improvement over previously reported oncoretrovirus vectors for Agamma-globin, and demonstrates the capacity of the HPFH2 enhancer to abrogate sequence-autonomous silencing of the Agamma-globin promoter in the context of a gene transfer vector.
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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.