ArticleMolecular therapy : the journal of the American Society of Gene Therapy2008
Double oxygen-sensing vector system for robust hypoxia/ischemia-regulated gene induction in cardiac muscle in vitro and in vivo.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Genetically Encoded Tools for Research of Cell Signaling and Metabolism under Brain Hypoxia.Antioxidants (Basel, Switzerland) · 2020Review
- A genetically encoded biosensor for visualising hypoxia responsesBiology open · 2017Article
- A novel family of fluorescent hypoxia sensors reveal strong heterogeneity in tumor hypoxia at the cellular level.The EMBO journal · 2016Article
- Upregulation of cardioprotective SUR2A by sub-hypoxic drop in oxygen.Biochimica et biophysica acta · 2014Article
- Differential effects of S100 proteins A2 and A6 on cardiac Ca(2+) cycling and contractile performance.Journal of molecular and cellular cardiology · 2014Article
- Gene therapy for heart failure.Circulation research · 2012Review
- Multimodality imaging of hypoxia in preclinical settings.The quarterly journal of nuclear medicine and molecular imaging : official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of... · 2010Review
- Article
- Molecular cardiology in translation: gene, cell and chemical-based experimental therapeutics for the failing heart.Journal of cardiovascular translational research · 2008Review
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Authors and funding
7 authors.
Funding
Abstract
High-fidelity genetically encoded bio-sensors that respond to changes in cellular environmental milieu in disease offer great potential in a range of patho-physiological settings. Here a unique hypoxia-regulated vector-based system with double oxygen-sensing transcriptional elements was developed for rapid and robust hypoxia-regulated gene expression in the heart. Hypoxia-responsive cis elements were used in tandem with a single proline-modified oxygen-dependent degradation (ODD) domain of hypoxia-inducible factor-1alpha to form a double oxygen-sensing vector system (DOSVS). In adult cardiac myocytes in vitro, the DOSVS demonstrated a low background expression not different from baseline control in normoxia, and with 100% efficiency, robust, 1,000-fold induction upon hypoxia. In the heart in vivo, hypoxic and ischemic challenges elicited rapid 700-fold induction in living animals, exceeding that obtained by a high-fidelity constitutive cytomegalovirus (CMV) viral promoter. DOSVS also showed high temporal resolution in the heart in response to cyclical bouts of hypoxia in vivo. We propose that DOSVS will be valuable for a range of applications, including bio-sensing and therapeutic gene expression in the heart and other organ systems that are confronted by chronic or episodic hypoxic/ischemic stresses in vivo.
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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.