ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Use of miRNA response sequences to block off-target replication and increase the safety of an unattenuated, glioblastoma-targeted oncolytic HSV.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 68 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
68 citing papers in PubMed, 92 citations in OpenAlex.
- Syncytium-forming HSV-1 in cancer gene therapy: From molecular mechanisms to clinical translation.Virulence · 2026Review
- mRNA vaccine immunity is enhanced by hepatocyte detargeting and not dependent on dendritic cell expression.Nature biotechnology · 2026Article
- MicroRNA-138 regulation promotes the efficacy of oncolytic herpes virus G47Δ for malignant brain tumor therapy.Molecular therapy. Oncology · 2026Article
- Engineering HSV-1 for oncolytic therapy: From molecular entry mechanisms to retargeting strategies.Genes & diseases · 2026Review
- Gene Therapy: Transforming the Battle Against Pancreatic Cancer.Current gene therapy · 2026Review
- Oncolytic viruses in head and neck cancer: therapeutic promise and translational challenges.Frontiers in immunology · 2026Review
- Retargeted oncolytic viruses engineered to remodel the tumor microenvironment for glioblastoma immunotherapy.Nature cancer · 2025Article
- Targeting and tracking mRNA lipid nanoparticles at the particle, transcript and protein level.Nature biomedical engineering · 2025Review
- An oncolytic herpes simplex virus armed with IL-12 for treatment of preclinical glioblastoma.Molecular therapy. Oncology · 2025Article
- Exploring LAT-derived miRNAs as regulatory agents of EphrinA3 in glioblastoma multiforme.Biochemistry and biophysics reports · 2025Article
- Extracellular vesicles as missiles for enhanced anti-tumor efficacy of oncolytic viruses: from disseminating oncolysis and anti-tumor immunity to targeted delivery.Cell communication and signaling : CCS · 2025Review
- Oncolytic viruses as cancer therapeutics: From mechanistic insights to clinical translation.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Viral and cellular insulators promote sustained HSV vector-mediated transgene expression in brain.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Integrating system biology and intratumor gene therapy by trans-complementing the appropriate co-stimulatory molecule as payload in oncolytic herpes virus.Cancer gene therapy · 2024Article
- miRNA-Mediated Mechanisms in the Generation of Effective and Safe Oncolytic Viruses.Pharmaceutics · 2024Review
- Oncolytic herpes simplex viruses designed for targeted treatment of EGFR-bearing tumors.Molecular therapy. Oncology · 2024Article
- Disease-modifying rdHSV-CA8* non-opioid analgesic gene therapy treats chronic osteoarthritis pain by activating Kv7 voltage-gated potassium channels.Frontiers in molecular neuroscience · 2024Article
- rdHSV-CA8 non-opioid analgesic gene therapy decreases somatosensory neuronal excitability by activating Kv7 voltage-gated potassium channels.Frontiers in molecular neuroscience · 2024Article
- Novel Therapies in Glioblastoma Treatment: Review of Glioblastoma; Current Treatment Options; and Novel Oncolytic Viral Therapies.Medical sciences (Basel, Switzerland) · 2023Review
- Oncolytic Viruses in the Era of Omics, Computational Technologies, and Modeling: Thesis, Antithesis, and Synthesis.International journal of molecular sciences · 2023Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issuedCorrigendum to "Use of miRNA response sequences to block off-target replication and increase the safety of an unattenuated, glioblastoma-targeted oncolytic HSV".2015 · Chiocca, Nino [corrected to Chiocca, Ennio A]
Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
Abstract
Glioblastoma multiforme (GBM) is an aggressive brain cancer for which there is no effective treatment. Oncolytic HSV vectors (oHSVs) are attenuated lytic viruses that have shown promise in the treatment of human GBM models in animals, but their efficacy in early phase patient trials has been limited. Instead of attenuating the virus with mutations in virulence genes, we engineered four copies of the recognition sequence for miR-124 into the 3'UTR of the essential ICP4 gene to protect healthy tissue against lytic virus replication; miR-124 is expressed in neurons but not in glioblastoma cells. Following intracranial inoculation into nude mice, the miR-124-sensitive vector failed to replicate or show overt signs of pathogenesis. To address the concern that this safety feature may reduce oncolytic activity, we inserted the miR-124 response elements into an unattenuated, human receptor (EGFR/EGFRvIII)-specific HSV vector. We found that miR-124 sensitivity did not cause a loss of treatment efficiency in an orthotopic model of primary human GBM in nude mice. These results demonstrate that engineered miR-124 responsiveness can eliminate off-target replication by unattenuated oHSV without compromising oncolytic activity, thereby providing increased safety.
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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.