ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Genomic and functional assays demonstrate reduced gammaretroviral vector genotoxicity associated with use of the cHS4 chromatin insulator.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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Who cites it
37 citing papers in PubMed, 63 citations in OpenAlex.
- Spectrum, pathobiology, mechanistic insights and diagnostic challenges of post-CAR T cell therapy lymphoproliferative disorders.Nature reviews. Clinical oncology · 2026Review
- Cancer gene therapy: historical perspectives, current applications, and future directions.Functional & integrative genomics · 2025Review
- Genomic context sensitivity of insulator function.Genome research · 2022Article
- Investigating the Barrier Activity of Novel, Human Enhancer-Blocking Chromatin Insulators for Hematopoietic Stem Cell Gene Therapy.Human gene therapy · 2021Article
- Sustained transgene expression from sleeping beauty DNA transposons containing a core fragment of the HNRPA2B1-CBX3 ubiquitous chromatin opening element (UCOE).BMC biotechnology · 2019Article
- Gene Therapy for β-Hemoglobinopathies.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Review
- Evidence for the in vivo safety of insulated foamy viral vectors.Gene therapy · 2017Article
- Retroviral vector interactions with hematopoietic cells.Current opinion in virology · 2016Review
- Insulators to Improve the Safety of Retroviral Vectors for HIV Gene Therapy.Biomedicines · 2016Article
- Insulated Foamy Viral Vectors.Human gene therapy · 2016Article
- A comparison of foamy and lentiviral vector genotoxicity in SCID-repopulating cells shows foamy vectors are less prone to clonal dominance.Molecular therapy. Methods & clinical development · 2016Article
- Gene therapy for hemoglobin disorders - a mini-review.Journal of rare diseases research & treatment · 2016Article
- Genomic discovery of potent chromatin insulators for human gene therapy.Nature biotechnology · 2015Article
- An insulator element located at the cyclin B1 interacting protein 1 gene locus is highly conserved among mammalian species.PloS one · 2015Article
- Uncovering and dissecting the genotoxicity of self-inactivating lentiviral vectors in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- A chimeric HS4-SAR insulator (IS2) that prevents silencing and enhances expression of lentiviral vectors in pluripotent stem cells.PloS one · 2014Article
- Foamy virus vectors for HIV gene therapy.Viruses · 2013Review
- A review of therapeutic prospects of non-viral gene therapy in the retinal pigment epithelium.Biomaterials · 2013Review
- Lack of genotoxicity due to foamy virus vector integration in human iPSCs.Gene therapy · 2013Article
- Hematopoietic stem cell gene therapy:assessing the relevance of preclinical models.Seminars in hematology · 2013Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Interest in the use of recombinant retroviral vectors for clinical gene therapy has been tempered by evidence of vector-mediated genotoxicity involving the activation of cellular oncogenes flanking sites of vector integration. We report here that the rate of gammaretroviral vector genotoxicity can be significantly reduced by addition of the cHS4 chromatin insulator, based on two complementary approaches for assessing vector-mediated genotoxicity. One approach involves the direct, genomewide assessment of cellular gene dysregulation using panels of transduced cell clones and genomic microarrays, whereas the other involves the functional assessment of malignant transformation using a factor-dependent cell line. Both assays are robust and quantitative, and indicate the cHS4 chromatin insulator can reduce vector-mediated genotoxicity approximately sixfold (ranged three to eight fold). These approaches also provide a means for assessing various aspects of vector-mediated genotoxicity, including the overall rate of cellular gene dysregulation, the potential influence of vector provirus over large genomic distances, and the involvement of oncogenic pathways in vector-mediated malignant transformation.
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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.