ArticleHuman gene therapy methods2013
The chicken hypersensitivity site 4 core insulator blocks promoter interference in lentiviral vectors.
Article in Human gene therapy methods, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Highly multiplexed mammalian metabolic engineering with a shotgun approach.Nature biotechnology · 2026Article
- Genomic Context and Insert Orientation in the Regulation of Transgene Expression in Adenoviral Vectors.International journal of molecular sciences · 2026Review
- Analog epigenetic memory revealed by targeted chromatin editing.Cell genomics · 2025Article
- Control of Multigene Expression Stoichiometry in Mammalian Cells Using Synthetic Promoters.ACS synthetic biology · 2021Article
- Characterization of the cHS4 insulator in mouse embryonic stem cells.FEBS open bio · 2020Article
- Article
- Development of a forward-oriented therapeutic lentiviral vector for hemoglobin disorders.Nature communications · 2019Article
- Spontaneous reactivation of latent HIV-1 promoters is linked to the cell cycle as revealed by a genetic-insulators-containing dual-fluorescence HIV-1-based vector.Scientific reports · 2018Article
- Adenoviral Type 35 and 26 Vectors with a Bidirectional Expression Cassette in the E1 Region Show an Improved Genetic Stability Profile and Potent Transgene-Specific Immune Response.Human gene therapy · 2018Article
- Progresses towards safe and efficient gene therapy vectors.Oncotarget · 2015Review
- Genomic discovery of potent chromatin insulators for human gene therapy.Nature biotechnology · 2015Article
- Increased Specific Labeling of INS-1 Pancreatic Beta-Cell by Using RIP-Driven Cre Mutants with Reduced Activity.PloS one · 2015Article
- Evaluation of engraftment and immunological tolerance after reduced intensity conditioning in a rhesus hematopoietic stem cell gene therapy model.Gene therapy · 2014Article
- Decitabine suspends human CD34+ cell differentiation and proliferation during lentiviral transduction.PloS one · 2014Article
- Chicken β-globin insulators fail to shield the nkx2.5 promoter from integration site effects in zebrafish.Molecular genetics and genomics : MGG · 2013Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Lentiviral vectors, including double internal promoters, can be used to express two transgenes in a single vector construct; however, transcriptional activities from double internal promoters are often inhibited by promoter interference. To determine whether the chicken hypersensitivity site 4 insulator (cHS4) could block promoter interference, lentiviral vectors including an MSCV-U3 promoter (Mp) and an EF1α promoter (Ep) were generated, and transgene expression was evaluated among transduced cells. In the Ep-Mp configuration, transcriptional activity from Mp was much lower, while Mp-Ep had similar transcription levels from both promoters. The cHS4 core insulator increased expression levels from Mp in HeLa cells, hematopoietic cell lines, and mouse peripheral blood cells following hematopoietic stem cell transplantation transduced with the Mp-Ep configured vector. This blocking function was mainly mediated by barrier activity regions in the insulator but not by CCCTC-binding factor (CTCF) binding sites. Cytosine-phosphate-guanine (CpG) methylation did not contribute to this barrier activity. In summary, combining the cHS4 insulator in double promoter vectors can improve transgene expression levels in various cell lines and mouse hematopoietic repopulating cells. These findings are useful for developing hematopoietic stem cell gene therapy.
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