ArticleBMC biotechnology2009
Incorporating double copies of a chromatin insulator into lentiviral vectors results in less viral integrants.
Article in BMC biotechnology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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19 citing papers in PubMed, 34 citations in OpenAlex.
- Engineering high-titer lentiviral vectors for robust expression of RNA-based gene circuits.bioRxiv : the preprint server for biology · 2026Article
- Preclinical efficacy of a modified gamma-globin lentivirus gene therapy in Berkeley sickle cell anemia mice and human xenograft models.Molecular therapy. Methods & clinical development · 2025Article
- The sound of silence: Transgene silencing in mammalian cell engineering.Cell systems · 2022Review
- Identification of SSEA-1 expressing enhanced reprogramming (SEER) cells in porcine embryonic fibroblasts.Cell cycle (Georgetown, Tex.) · 2017Article
- Systematic in vitro and in vivo characterization of Leukemia-inhibiting factor- and Fibroblast growth factor-derived porcine induced pluripotent stem cells.Molecular reproduction and development · 2017Article
- Insulated Foamy Viral Vectors.Human gene therapy · 2016Article
- Insulators to Improve the Safety of Retroviral Vectors for HIV Gene Therapy.Biomedicines · 2016Article
- Current and future alternative therapies for beta-thalassemia major.Biomedical journal · 2016Review
- Gene Therapy of the β-Hemoglobinopathies by Lentiviral Transfer of the β(A(T87Q))-Globin Gene.Human gene therapy · 2016Article
- A minimal ubiquitous chromatin opening element (UCOE) effectively prevents silencing of juxtaposed heterologous promoters by epigenetic remodeling in multipotent and pluripotent stem cells.Nucleic acids research · 2015Article
- Preclinical evaluation of efficacy and safety of an improved lentiviral vector for the treatment of β-thalassemia and sickle cell disease.Current gene therapy · 2015Article
- Long-term reproducible expression in human fetal liver hematopoietic stem cells with a UCOE-based lentiviral vector.PloS one · 2014Article
- A review of therapeutic prospects of non-viral gene therapy in the retinal pigment epithelium.Biomaterials · 2013Review
- Prototypic chromatin insulator cHS4 protects retroviral transgene from silencing in Schistosoma mansoni.Transgenic research · 2012Article
- Influence of insulators on transgene expression from integrating and non-integrating lentiviral vectors.Genetic vaccines and therapy · 2011Article
- The GATA1-HS2 enhancer allows persistent and position-independent expression of a β-globin transgene.PloS one · 2011Article
- A general chemical method to regulate protein stability in the mammalian central nervous system.Chemistry & biology · 2010Article
- A ubiquitous chromatin opening element (UCOE) confers resistance to DNA methylation-mediated silencing of lentiviral vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2010Article
- Possible applications for replicating HIV 1 vectors.HIV therapy · 2010Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundLentiviral vectors hold great promise as gene transfer vectors in gene therapeutic settings. However, problems related to the risk of insertional mutagenesis, transgene silencing and positional effects have stalled the use of such vectors in the clinic. Chromatin insulators are boundary elements that can prevent enhancer-promoter interactions, if placed between these elements, and protect transgene cassettes from silencing and positional effects. It has been suggested that insulators can improve the safety and performance of lentiviral vectors. Therefore insulators have been incorporated into lentiviral vectors in order to enhance their safety profile and improve transgene expression. Commonly such insulator vectors are produced at lower titers than control vectors thus limiting their potential use.
resultsIn this study we cloned in tandem copies of the chicken beta-globin insulator (cHS4) on both sides of the transgene cassette in order to enhance the insulating effect. Our insulator vectors were produced at significantly lower titers compared to control vectors, and we show that this reduction in titer is due to a block during the transduction process that appears after reverse transcription but before integration of the viral DNA. This non-integrated viral DNA could be detected by PCR and, importantly, prevented efficient transduction of target cells.
conclusionThese results have importance for the future use of insulator sequences in lentiviral vectors and might limit the use of insulators in vectors for in vivo use. Therefore, a careful analysis of the optimal design must be performed before insulators are included into clinical lentiviral vectors.
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