ArticleGene therapy2000
Development of a hypoxia-responsive vector for tumor-specific gene therapy.
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 94 papers.
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Who cites it
94 citing papers in PubMed, 265 citations in OpenAlex.
- Chemotherapy alleviates subacute recurrent glioma-associated refractory cerebral edema by downregulating vascular endothelial growth factor.Medical oncology (Northwood, London, England) · 2014Trial
- Ultrasound priming gated by solid tumor hallmarks to guide CAR-T therapy.Science advances · 2026Article
- PHGDH loss promotes hypoxia tolerance through glycolytic reprogramming and enhanced HIF-1 activity.Cell death discovery · 2026Article
- Envirotune-CAR-T: a hypoxia-responsive and glutamine-enhanced CAR-T cell therapy for overcoming tumor microenvironment-mediated suppression.Journal for immunotherapy of cancer · 2025Article
- In Vitro Sonodynamic Therapy Using a High Throughput 3D Glioblastoma Spheroid Model with 5-ALA and TMZ Sonosensitizers.Advanced healthcare materials · 2024Article
- Review
- Genetically Encoded Reporters to Monitor Hypoxia.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Systemic Delivery of Magnetogene Nanoparticle Vector for Gene Expression in Hypoxic Tumors.Pharmaceutics · 2023Article
- Targeted RASSF1A expression inhibits proliferation of HER2‑positive breast cancer cellsExperimental and therapeutic medicine · 2023Article
- The therapeutic effect of PEI-FeFrontiers in oncology · 2023Article
- Hypoxia-directed tumor targeting of CRISPR-Cas9 and HSV-TK suicide gene therapy using lipid nanoparticles.Molecular therapy. Methods & clinical development · 2022Article
- High throughput screen for the improvement of inducible promoters for tumor microenvironment cues.Scientific reports · 2022Article
- Gene Therapy in Orthopaedics: Progress and Challenges in Pre-Clinical Development and Translation.Frontiers in bioengineering and biotechnology · 2022Review
- Cell line development for continuous high cell density biomanufacturing: Exploiting hypoxia for improved productivity.Metabolic engineering communications · 2021Article
- Hypoxia Triggers the Intravasation of Clustered Circulating Tumor Cells.Cell reports · 2020Article
- Reversal of Hypoxic Pulmonary Hypertension by Hypoxia-Inducible Overexpression of Angiotensin-(1-7) in Pulmonary Endothelial Cells.Molecular therapy. Methods & clinical development · 2020Article
- Genetically Encoded Tools for Research of Cell Signaling and Metabolism under Brain Hypoxia.Antioxidants (Basel, Switzerland) · 2020Review
- Molecular and functional imaging insights into the role of hypoxia in cancer aggression.Cancer metastasis reviews · 2019Review
- Insights into Hypoxia: Non-invasive Assessment through Imaging Modalities and Its Application in Breast Cancer.Journal of breast cancer · 2019Review
- 4-O-Methylascochlorin inhibits the prolyl hydroxylation of hypoxia-inducible factor-1α, which is attenuated by ascorbate.The Journal of antibiotics · 2019Article
34 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
We are developing new gene therapy vectors whose expression is selectively activated by hypoxia, a unique feature of human solid tumors. As vascular endothelial growth factor (VEGF) is upregulated by hypoxia, such regulatory mechanisms would enable us to achieve hypoxia-inducible expression of therapeutic genes. Constructs with five copies of hypoxia-responsive elements (HREs) derived from the 5'-untranslated region (UTR) of the human VEGF showed excellent transcriptional activation at low oxygen tension relevant to tumor hypoxia. In an attempt to achieve higher responsiveness, various combinations of HREs and promoters were examined. In addition, we also investigated whether the 3' UTR of the VEGF gene would confer increased post-transcriptional mRNA stability under hypoxic conditions. However, despite increases in the hypoxic/aerobic ratio of luciferase activity, gene expression with 3' UTR was lower due to mRNA destabilization by AU-rich elements (AREs). Thus, we found no benefit from the inclusion of the 3' UTR in our vectors. Of all the vectors tested, the combination of 5HRE and a CMV minimal promoter exhibited hypoxia responsiveness (over 500-fold) to the similar level to the intact CMV promoter. We propose that this vector would be useful for tumor selective gene therapy.
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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.