ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
A ubiquitous chromatin opening element (UCOE) confers resistance to DNA methylation-mediated silencing of lentiviral vectors.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
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Who cites it
78 citing papers in PubMed, 130 citations in OpenAlex.
- UCOE-Mediated Transcriptional Stabilization Combined with EGFP-Based FACS Screening Enables Efficient Selection of High-Producing CHO Cells.Molecular biotechnology · 2026Article
- Lights up on the embryonic dance: tools and applications of optogenetics in developmental biology.Genes & development · 2026Review
- Phenotypic CRISPR screens identify NLRX1 as an essential activator of the human mitochondrial permeability transition.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Human Genome Safe Harbor Sites: A Comprehensive Review of Criteria, Discovery, Features, and Applications.Cells · 2026Review
- Termination sequence between an inducible promoter and ubiquitous chromatin opening element (UCOE) reduces gene expression leakage and silencing.Journal of biological engineering · 2025Article
- Assessment of non-myelotoxic agents as a preparatory regimen for hematopoietic stem cell gene therapy.Human cell · 2024Article
- An induced pluripotent stem cell line carrying a silencing-resistant calcium reporter allele.Stem cell research · 2024Article
- Implementation of ubiquitous chromatin opening elements as artificial integration sites for CRISPR/Cas9-mediated knock-in in mammalian cells.Engineering in life sciences · 2023Article
- A Ubiquitous Chromatin Opening Element and DNA Demethylation Facilitate Doxycycline-Controlled Expression during Differentiation and in Transgenic Mice.ACS synthetic biology · 2023Article
- Use of ubiquitous chromatin opening elements (UCOE) as tools to maintain transgene expression in biotechnology.Computational and structural biotechnology journal · 2023Review
- Delivering genes with human immunodeficiency virus-derived vehicles: still state-of-the-art after 25 years.Journal of biomedical science · 2022Review
- Endogenous spacing enables co-processing of microRNAs and efficient combinatorial RNAi.Cell reports methods · 2022Article
- Effects of ubiquitous chromatin opening element (UCOE) on recombinant anti-TNFα antibody production and expression stability in CHO-DG44 cells.Cytotechnology · 2022Article
- CRISPR-Mediated Genomic Addition to CPS1 Deficient iPSCs is Insufficient to Restore Nitrogen Homeostasis.The Yale journal of biology and medicine · 2021Article
- Effective, safe, and sustained correction of murine XLA using a UCOE-BTK promoter-based lentiviral vector.Molecular therapy. Methods & clinical development · 2021Article
- Therapeutic Angiogenesis by a "Dynamic Duo": Simultaneous Expression of HGF and VEGF165 by Novel Bicistronic Plasmid Restores Blood Flow in Ischemic Skeletal Muscle.Pharmaceutics · 2020Article
- Dosing and Re-Administration of Lentiviral Vector forMolecular therapy. Methods & clinical development · 2020Article
- Rosa26 docking sites for investigating genetic circuit silencing in stem cells.Synthetic biology (Oxford, England) · 2020Article
- 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 Tools for Brain Diseases.Frontiers in pharmacology · 2019Review
18 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
DNA methylation may restrict the activity of gene transfer vectors due to inadvertent silencing. In P19 embryonic carcinoma cells in vitro, we found that transgene expression regulated by the SFFV LTR and EF1 alpha promoter declined rapidly within 16 days, but for A2UCOE derived from the human HNRPA2B1-CBX3 housekeeping gene locus, remained completely stable. Silencing correlated with extensive epigenetic methylation of CpG sites, whereas the A2UCOE was almost completely resistant. Linking of the A2UCOE upstream of the SFFV LTR protected this element from both DNA methylation and silencing. Analysis of engrafted hematopoietic cells in vivo transduced with the same vectors revealed a similar pattern. The A2UCOE displayed little or no methylation in either primary or secondary graft recipients, and gene expression profiles were highly conserved between the two groups. These studies provide convincing evidence that DNA methylation plays a direct role in regulating self-inactivating (SIN) lentiviral transgene expression, and that the stability of expression from the A2UCOE is, at least in part, due to methylation resistance. The A2UCOE therefore has considerable utility for gene therapy applications where reliable and sustained gene expression is desirable.
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