ArticleProceedings of the National Academy of Sciences of the United States of America2000
Preselection of retrovirally transduced bone marrow avoids subsequent stem cell gene silencing and age-dependent extinction of expression of human beta-globin in engrafted mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 83 citations in OpenAlex.
- Investigating the Barrier Activity of Novel, Human Enhancer-Blocking Chromatin Insulators for Hematopoietic Stem Cell Gene Therapy.Human gene therapy · 2021Article
- Gene Therapy For Beta-Thalassemia: Updated Perspectives.The application of clinical genetics · 2019Article
- Ex Vivo Selection of Transduced Hematopoietic Stem Cells for Gene Therapy of β-Hemoglobinopathies.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Extensive methylation of promoter sequences silences lentiviral transgene expression during stem cell differentiation in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Gene therapy: light is finally in the tunnel.Protein & cell · 2011Review
- Gene therapy in thalassemia and hemoglobinopathies.Mediterranean journal of hematology and infectious diseases · 2009Article
- Article
- Transient in vivo beta-globin production after lentiviral gene transfer to hematopoietic stem cells in the nonhuman primate.Human gene therapy · 2009Article
- Myoblasts and macrophages share molecular components that contribute to cell-cell fusion.The Journal of cell biology · 2008Article
- Gene therapy approaches for stem cell protection.Gene therapy · 2008Review
- Candidate genes for expansion and transformation of hematopoietic stem cells by NUP98-HOX fusion genes.PloS one · 2007Article
- Long-term gene expression in dividing and nondividing cells using SV40-derived vectors.Molecular biotechnology · 2006Review
- Hematopoietic stem cell gene therapy with drug resistance genes: an update.Cancer gene therapy · 2005Review
- High-level beta-globin expression and preferred intragenic integration after lentiviral transduction of human cord blood stem cells.The Journal of clinical investigation · 2004Article
- Evaluation of optimal expression cassette in retrovirus vector for beta-thalassemia gene therapy.Molecular biotechnology · 2003Article
- Permanent and panerythroid correction of murine beta thalassemia by multiple lentiviral integration in hematopoietic stem cells.Proceedings of the National Academy of Sciences of the United States of America · 2002Article
- Persisting multilineage transgene expression in the clonal progeny of a hematopoietic stem cell.Leukemia · 2002Article
- Efficient marking of neural stem cell-derived neurons with a modified murine embryonic stem cell virus, MESV2.Gene therapy · 2002Article
- Optimized lentiviral transduction of erythroid precursors from healthy adults and patients with myelodysplastic syndromes.Leukemia · 2002Article
- Hematopoietic stem cell gene therapy.International journal of hematology · 2002Review
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10 authors at 2 institutions in 1 country.
Funding
Abstract
Transcriptional silencing of genes transferred into hematopoietic stem cells poses one of the most significant challenges to the success of gene therapy. If the transferred gene is not completely silenced, a progressive decline in gene expression as the mice age often is encountered. These phenomena were observed to various degrees in mouse transplant experiments using retroviral vectors containing a human beta-globin gene, even when cis-linked to locus control region derivatives. Here, we have investigated whether ex vivo preselection of retrovirally transduced stem cells on the basis of expression of the green fluorescent protein driven by the CpG island phosphoglycerate kinase promoter can ensure subsequent long-term expression of a cis-linked beta-globin gene in the erythroid lineage of transplanted mice. We observed that 100% of mice (n = 7) engrafted with preselected cells concurrently expressed human beta-globin and the green fluorescent protein in 20-95% of their RBC for up to 9.5 mo posttransplantation, the longest time point assessed. This expression pattern was successfully transferred to secondary transplant recipients. In the presence of beta-locus control region hypersensitive site 2 alone, human beta-globin mRNA expression levels ranged from 0.15% to 20% with human beta-globin chains detected by HPLC. Neither the proportion of positive blood cells nor the average expression levels declined with time in transplanted recipients. Although suboptimal expression levels and heterocellular position effects persisted, in vivo stem cell gene silencing and age-dependent extinction of expression were avoided. These findings support the further investigation of this type of vector for the gene therapy of human hemoglobinopathies.
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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.