ArticleMolecular therapy : the journal of the American Society of Gene Therapy2009
Mutant sodium channel for tumor therapy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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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.
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Who cites it
11 citing papers in PubMed, 16 citations in OpenAlex.
- Herpes Simplex Virus: A Versatile Tool for Insights Into Evolution, Gene Delivery, and Tumor Immunotherapy.Virology : research and treatment · 2020Review
- Sodium homeostasis in the tumour microenvironment.Biochimica et biophysica acta. Reviews on cancer · 2019Review
- Function and Dysfunction of TMC Channels in Inner Ear Hair Cells.Cold Spring Harbor perspectives in medicine · 2019Review
- Comparison of fluorescence probes for intracellular sodium imaging in prostate cancer cell lines.European biophysics journal : EBJ · 2016Article
- ENaCs and ASICs as therapeutic targets.American journal of physiology. Cell physiology · 2012Review
- Lanatoside C sensitizes glioblastoma cells to tumor necrosis factor-related apoptosis-inducing ligand and induces an alternative cell death pathway.Neuro-oncology · 2011Article
- In vivo cell death mediated by synthetic ion channels.Chemical communications (Cambridge, England) · 2011Article
- Amiloride docking to acid-sensing ion channel-1.The Journal of biological chemistry · 2010Article
- Herpes Virus Amplicon Vectors.Viruses · 2009Article
- Tannous et al. Respond.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Article
- Rapid tumor cell swelling and bursting: beware of collateral damage.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Article
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Authors and funding
12 authors at 6 institutions in 2 countries.
Funding
Abstract
Viral vectors have been used to deliver a wide range of therapeutic genes to tumors. In this study, a novel tumor therapy was achieved by the delivery of a mammalian brain sodium channel, ASIC2a, carrying a mutation that renders it constitutively open. This channel was delivered to tumor cells using a herpes simplex virus-1/Epstein-Barr virus (HSV/EBV) hybrid amplicon vector in which gene expression was controlled by a tetracycline regulatory system (tet-on) with silencer elements. Upon infection and doxycycline induction of mutant channel expression in tumor cells, the open channel led to amiloride-sensitive sodium influx as assessed by patch clamp recording and sodium imaging in culture. Within hours, tumor cells swelled and died. In addition to cells expressing the mutant channel, adjacent, noninfected cells connected by gap junctions also died. Intratumoral injection of HSV/EBV amplicon vector encoding the mutant sodium channel and systemic administration of doxycycline led to regression of subcutaneous tumors in nude mice as assessed by in vivo bioluminescence imaging. The advantage of this direct mode of tumor therapy is that all types of tumor cells become susceptible and death is rapid with no time for the tumor cells to become resistant.
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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.