ArticleGene therapy2000
Insulation from viral transcriptional regulatory elements improves inducible transgene expression from adenovirus vectors in vitro and in vivo.
Article in Gene therapy, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
47 citing papers in PubMed, 119 citations in OpenAlex.
- Genomic Context and Insert Orientation in the Regulation of Transgene Expression in Adenoviral Vectors.International journal of molecular sciences · 2026Review
- Integrase-Deficient Lentiviral Vector as a Platform for Efficient CRISPR/Cas9-Mediated Gene Editing for Mucopolysaccharidosis IVA.International journal of molecular sciences · 2025Article
- Transcription Factor Binding Site in Promoter Determines the Pattern of Plasmid-Based Transgene Expression In Vivo.Pharmaceutics · 2024Article
- Improvement of HSV-1 based amplicon vectors for a safe and long-lasting gene therapy in non-replicating cells.Molecular therapy. Methods & clinical development · 2021Article
- Retargeting adenoviruses for therapeutic applications and vaccines.FEBS letters · 2020Review
- The M4 insulator, the TM2 matrix attachment region, and the double copy of the heavy chain gene contribute to the enhanced accumulation of the PHB-01 antibody in tobacco plants.Transgenic research · 2020Article
- Transcatheter arterial embolization combined with hypoxia-replicative oncolytic adenovirus perfusion enhances the therapeutic effect of hepatic carcinoma.Cancer management and research · 2019Article
- Targeted in vivo knock-in of human alpha-1-antitrypsin cDNA using adenoviral delivery of CRISPR/Cas9.Gene therapy · 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
- Transcriptional Targeting of Mature Dendritic Cells with Adenoviral Vectors via a Modular Promoter System for Antigen Expression and Functional Manipulation.Journal of immunology research · 2016Article
- Lentiviral Vectors Mediate Long-Term and High Efficiency Transgene Expression in HEK 293T cells.International journal of medical sciences · 2015Article
- Methods for gene transfer to the central nervous system.Advances in genetics · 2014Review
- The chicken hypersensitivity site 4 core insulator blocks promoter interference in lentiviral vectors.Human gene therapy methods · 2013Article
- Article
- Adenoviral insulinoma-associated protein 1 promoter-driven suicide gene therapy with enhanced selectivity for treatment of neuroendocrine cancers.Ochsner journal · 2013Article
- Compound screening platform using human induced pluripotent stem cells to identify small molecules that promote chondrogenesis.Protein & cell · 2012Article
- Modifications to the INSM1 promoter to preserve specificity and activity for use in adenoviral gene therapy of neuroendocrine carcinomas.Cancer gene therapy · 2012Article
- Minimizing the unpredictability of transgene expression in plants: the role of genetic insulators.Plant cell reports · 2012Review
- Analysis of the enhancer-blocking function of the TBS element from Petunia hybrida in transgenic Arabidopsis thaliana and Nicotiana tabacum.Plant cell reports · 2011Article
- The use of chromatin insulators to improve the expression and safety of integrating gene transfer vectors.Human gene therapy · 2011Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Recombinant adenoviruses (Ad) are attractive vectors for gene transfer in vitro and in vivo. However, the widely used E1-deleted vectors as well as newer generation vectors contain viral sequences, including transcriptional elements for viral gene expression. These viral regulatory elements can interfere with heterologous promoters used to drive transgene expression and may impair tissue-specific or inducible transgene expression. This study demonstrates that the activity of a metal-inducible promoter is affected by Ad sequences both upstream and downstream of the transgene cassette in both orientations. Interference with expression from the heterologous promoter was particularly strong by viral regulatory elements located within Ad sequences nucleotides 1-341. This region is present in all recombinant Ad vectors, including helper-dependent vectors. An insulator element derived from the chicken gamma-globin locus (HS-4) was employed to shield the inducible promoter from viral enhancers as tested after gene transfer with first-generation Ad vectors in vitro and in vivo. Optimal shielding was obtained when the transgene expression cassette was flanked on both sides by HS-4 elements, except for when the HS-4 element was placed in 3'-->5' orientation in front of the promoter. The insulators reduced basal expression to barely detectable levels in the non-induced stage, and allowed for induction factors of approximately 40 and approximately 230 in vitro and in vivo, respectively. Induction ratios from Ad vectors without insulators were approximately 40-fold lower in vitro and approximately 15-fold lower in vivo. This study proves the potential of insulators to improve inducible or tissue-specific gene expression from adenovirus vectors, which is important for studying gene functions as well as for gene therapy approaches. Furthermore, our data show that insulators exert enhancer-blocking effects in episomal DNA.
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Registered trials
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.