ArticlePloS one2009
The 3' region of the chicken hypersensitive site-4 insulator has properties similar to its core and is required for full insulator activity.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed.
- Lentiviral gene therapy with reduced-intensity conditioning for sickle cell disease: a phase 1/2 trial.Nature medicine · 2025Trial
- Lentiviral-Mediated Systemic RNA Interference In Vivo.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Lentiviral vectors for inducible, transactivator-free advanced therapy medicinal products: Application to CAR-T cells.Molecular therapy. Nucleic acids · 2023Article
- Improved Functionality of Integration-Deficient Lentiviral Vectors (IDLVs) by the Inclusion of ISPharmaceutics · 2021Article
- Long-Term Safety and Efficacy of Gene-Pulmonary Macrophage Transplantation Therapy of PAP in Csf2raMolecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- Gene Therapy For Beta-Thalassemia: Updated Perspectives.The application of clinical genetics · 2019Article
- The IS2 Element Improves Transcription Efficiency of Integration-Deficient Lentiviral Vector Episomes.Molecular therapy. Nucleic acids · 2018Article
- Safe and Effective Gene Therapy for Murine Wiskott-Aldrich Syndrome Using an Insulated Lentiviral Vector.Molecular therapy. Methods & clinical development · 2017Article
- Evidence for the in vivo safety of insulated foamy viral vectors.Gene therapy · 2017Article
- Gene Addition Strategies for β-Thalassemia and Sickle Cell Anemia.Advances in experimental medicine and biology · 2017Review
- Evaluating the Safety of Retroviral Vectors Based on Insertional Oncogene Activation and Blocked Differentiation in Cultured Thymocytes.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Insulators to Improve the Safety of Retroviral Vectors for HIV Gene Therapy.Biomedicines · 2016Article
- Insulated Foamy Viral Vectors.Human gene therapy · 2016Article
- Lentiviral Vectors Mediate Long-Term and High Efficiency Transgene Expression in HEK 293T cells.International journal of medical sciences · 2015Article
- Generation of a lentiviral vector producer cell clone for human Wiskott-Aldrich syndrome gene therapy.Molecular therapy. Methods & clinical development · 2015Article
- Recent trends in the gene therapy of β-thalassemia.Journal of blood medicine · 2015Review
- Pulmonary macrophage transplantation therapy.Nature · 2014Article
- Pseudotyped murine leukemia virus for schistosome transgenesis: approaches, methods and perspectives.Transgenic research · 2014Article
- Gene therapy for hemoglobinopathies: the state of the field and the future.Hematology/oncology clinics of North America · 2014Review
- A chimeric HS4-SAR insulator (IS2) that prevents silencing and enhances expression of lentiviral vectors in pluripotent stem cells.PloS one · 2014Article
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6 authors.
Funding
Abstract
Chromatin insulators separate active transcriptional domains and block the spread of heterochromatin in the genome. Studies on the chicken hypersensitive site-4 (cHS4) element, a prototypic insulator, have identified CTCF and USF-1/2 motifs in the proximal 250 bp of cHS4, termed the "core", which provide enhancer blocking activity and reduce position effects. However, the core alone does not insulate viral vectors effectively. The full-length cHS4 has excellent insulating properties, but its large size severely compromises vector titers. We performed a structure-function analysis of cHS4 flanking lentivirus-vectors and analyzed transgene expression in the clonal progeny of hematopoietic stem cells and epigenetic changes in cHS4 and the transgene promoter. We found that the core only reduced the clonal variegation in expression. Unique insulator activity resided in the distal 400 bp cHS4 sequences, which when combined with the core, restored full insulator activity and open chromatin marks over the transgene promoter and the insulator. These data consolidate the known insulating activity of the canonical 5' core with a novel 3' 400 bp element with properties similar to the core. Together, they have excellent insulating properties and viral titers. Our data have important implications in understanding the molecular basis of insulator function and design of gene therapy vectors.
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