ArticleMolecular vision2008
Robust hypoxia-selective regulation of a retinal pigment epithelium-specific adeno-associated virus vector.
Article in Molecular vision, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.
- Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays.International journal of molecular sciences · 2020Pooled it
- Review
- A simplified protocol to induce hypoxia in a standard incubator: A focus on retinal cells.Experimental eye research · 2023Article
- Anti-Scg3 Gene Therapy to Treat Choroidal Neovascularization in Mice.Biomedicines · 2023Article
- The role of hypoxia-inducible factors in neovascular age-related macular degeneration: a gene therapy perspective.Cellular and molecular life sciences : CMLS · 2020Review
- Suppression of Choroidal Neovascularization by AAV-Based Dual-Acting Antiangiogenic Gene Therapy.Molecular therapy. Nucleic acids · 2019Article
- The Different Facades of Retinal and Choroidal Endothelial Cells in Response to Hypoxia.International journal of molecular sciences · 2018Review
- Cell-specific gene therapy driven by an optimized hypoxia-regulated vector reduces choroidal neovascularization.Journal of molecular medicine (Berlin, Germany) · 2018Article
- Imaging rhodopsin degeneration in vivo in a new model of ocular ischemia in living mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- A hypoxia-responsive glial cell-specific gene therapy vector for targeting retinal neovascularization.Investigative ophthalmology & visual science · 2014Article
- Flavin mononucleotide-based fluorescent proteins function in mammalian cells without oxygen requirement.PloS one · 2012Article
- Hypoxia-regulated retinal glial cell-specific promoter for potential gene therapy in disease.Investigative ophthalmology & visual science · 2011Article
- Republished review: Gene therapy for ocular diseases.Postgraduate medical journal · 2011Article
- Nicotinamide mononucleotide adenylyltransferase is a stress response protein regulated by the heat shock factor/hypoxia-inducible factor 1alpha pathway.The Journal of biological chemistry · 2011Article
- Gene therapy for ocular diseases.The British journal of ophthalmology · 2011Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
purposeTo develop an hypoxia-regulated retinal pigment epithelium (RPE)-specific adeno-associated virus (AAV) gene transfer platform that exploits hypoxia as a physiologic trigger for an early antiangiogenic treatment strategy directed at arresting neovascularization in the eye.
methodsTissue-specific and hypoxia-regulated expression vectors were constructed with tandem combinations of hypoxia responsive elements and aerobically silenced elements (HRSE) that together induce gene expression in hypoxia and suppress it in normoxia. For RPE-specific expression, the HRSE and a (6x) HRE (hypoxia responsive element) oligomer were ligated upstream of the Rpe65 promoter in a pGL3 firefly luciferase plasmid (pGL3-HRSE-6xHRE-Rpe65). The cell specificity of this novel hybrid promoter was tested in human RPE (ARPE-19), human glioblastoma, rat C6 glioma, mouse hippocampal neurons, and human embryonic kidney cell lines. Expression of all cell types in normoxia, and following 40 h hypoxia, was analyzed by dual luciferase assay. After confirmation of its tissue-specificity and hypoxia-inducibility, the hybrid promoter construct was integrated into a replication-deficient AAV delivery system and tested for cell-selectivity and hypoxia-inducible green fluorescent protein (GFP) reporter expression.
resultsThe HRSE-6xHRE-Rpe65 promoter was highly selective for RPE cells, strongly induced in hypoxia, and similar in activation strength to the cytomegalovirus (CMV) promoter. The AAV.HRSE.6xHRE.Rpe65 vector induced robust GFP expression in hypoxic ARPE-19 cells, but elicited no GFP expression in hypoxia in other cell types or in normoxic ARPE-19 cells.
conclusionsThe hypoxia-regulated, aerobically-silenced RPE-targeting vector forms a platform for focal autoregulated delivery of antiangiogenic agents in hypoxic regions of the RPE. Such autoinitiated therapy provides a means for early intervention in choroidal neovascularization, when it is most sensitive to inhibition.
Indexed as
Identifiers
18334957PMC2268848W1552589332What OpenQuestion holds
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.