ArticlePloS one2010
Double-detargeted oncolytic adenovirus shows replication arrest in liver cells and retains neuroendocrine cell killing ability.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 55 citations in OpenAlex.
- In Vitro Sensitivity of Neuroendocrine Neoplasms to an Armed Oncolytic Measles Vaccine Virus.Cancers · 2024Article
- Infection of non-cancer cells: A barrier or support for oncolytic virotherapy?Molecular therapy oncolytics · 2022Review
- Advances in the Genetically Engineered KillerRed for Photodynamic Therapy Applications.International journal of molecular sciences · 2021Review
- Oncolytic Virotherapy: From Bench to Bedside.Frontiers in cell and developmental biology · 2021Review
- Review
- Review
- Review
- A Plutocratic Proposal: an ethical way for rich patients to pay for a place on a clinical trial.Journal of medical ethics · 2017Article
- Glutaredoxin-1 Deficiency Causes Fatty Liver and Dyslipidemia by Inhibiting Sirtuin-1.Antioxidants & redox signaling · 2017Article
- MicroRNA-regulated viral vectors for gene therapy.World journal of experimental medicine · 2016Review
- Retargeted oncolytic adenovirus displaying a single variable domain of camelid heavy-chain-only antibody in a fiber protein.Molecular therapy oncolytics · 2015Article
- An infection-enhanced oncolytic adenovirus secreting H. pylori neutrophil-activating protein with therapeutic effects on neuroendocrine tumors.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Role of microRNAs in hepatocellular carcinoma: a clinical perspective.OncoTargets and therapy · 2013Review
- Local sustained delivery of oncolytic adenovirus with injectable alginate gel for cancer virotherapy.Gene therapy · 2013Article
- Tat-PTD-modified oncolytic adenovirus driven by the SCG3 promoter and ASH1 enhancer for neuroblastoma therapy.Human gene therapy · 2013Article
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- MicroRNA silencing improves the tumor specificity of adenoviral transgene expression.Cancer gene therapy · 2012Article
- The somatostatin analogue octreotide inhibits growth of small intestine neuroendocrine tumour cells.PloS one · 2012Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundWe have previously developed an oncolytic serotype 5 adenovirus (Ad5) with chromogranin-A (CgA) promoter-controlled E1A expression, Ad[CgA-E1A], with the intention to treat neuroendocrine tumors, including carcinoids. Since carcinoids tend to metastasize to the liver it is important to fully repress viral replication in hepatocytes to avoid adenovirus-related liver toxicity. Herein, we explore miRNA-based regulation of E1A expression as a complementary mechanism to promoter-based transcriptional control. METHODOLOGY/PRINCIPAL
findingsAd[CgA-E1A-miR122], where E1A expression is further controlled by six tandem repeats of the target sequence for the liver-specific miR122, was constructed and compared to Ad[CgA-E1A]. We observed E1A suppression and replication arrest of the miR122-detargeted adenovirus in normal hepatocytes, while the two viruses killed carcinoid cells to the same degree. Repeated intravenous injections of Ad[CgA-E1A] induced liver toxicity in mice while Ad[CgA-E1A-miR122] injections did not. Furthermore, a miR122-detargeted adenovirus with the wild-type E1A promoter showed reduced replication in hepatic cells compared to wild-type Ad5 but not to the same extent as the miR122-detargeted adenovirus with the neuroendocrine-selective CgA promoter. CONCLUSIONS/SIGNIFICANCE: A combination of transcriptional (promoter) and post-transcriptional (miRNA target) regulation to control virus replication may allow for the use of higher doses of adenovirus for efficient tumors treatment without liver toxicity.
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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.