ArticleChinese journal of cancer research = Chung-kuo yen cheng yen chiu2013
Evaluation of miR-122-regulated suicide gene therapy for hepatocellular carcinoma in an orthotopic mouse model.
Article in Chinese journal of cancer research = Chung-kuo yen cheng yen chiu, 2013. 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, 10 citations in OpenAlex.
- Hypoxia-directed tumor targeting of CRISPR-Cas9 and HSV-TK suicide gene therapy using lipid nanoparticles.Molecular therapy. Methods & clinical development · 2022Article
- The Underlying Mechanisms of Noncoding RNAs in the Chemoresistance of Hepatocellular Carcinoma.Molecular therapy. Nucleic acids · 2020Review
- MicroRNA199a-Based Post-transcriptional Detargeting of Gene Vectors for Hepatocellular Carcinoma.Molecular therapy. Nucleic acids · 2018Article
- Article
- MicroRNA-Regulated Gene Delivery Systems for Research and Therapeutic Purposes.Molecules (Basel, Switzerland) · 2018Review
- miRNA122a regulation of gene therapy vectors targeting hepatocellular cancer stem cells.Oncotarget · 2018Article
- Management strategies for hepatocellular carcinoma: old certainties and new realities.Clinical and experimental medicine · 2016Review
- Effects of mesenchymal stromal cell-derived extracellular vesicles on tumor growth.Frontiers in immunology · 2014Review
- Design and development of a robotized system coupled to µCT imaging for intratumoral drug evaluation in a HCC mouse model.PloS one · 2014Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveIntratumoral administration of adenoviral vector encoding herpes simplex virus (HSV) thymidine kinase (TK) gene (Ad-TK) followed by systemic ganciclovir (GCV) is an effective approach in treating experimental hepatocellular carcinoma (HCC). However, hepatotoxicity due to unwanted vector spread and suicide gene expression limited the application of this therapy. miR-122 is an abundant, liver-specific microRNA whose expression is decreased in human primary HCC and HCC-derived cell lines. These different expression profiles provide an opportunity to induce tumor-specific gene expression by miR-122 regulation.
methodsBy inserting miR-122 target sequences (miR-122T) in the 3' untranslated region (UTR) of TK gene, we constructed adenovirus (Ad) vectors expressing miR-122-regulated TK (Ad-TK-122T) and report genes. After intratumoral administration of Ad vectors into an orthotopic miR-122-deficient HCC mouse model, we observed the miR-122-regulated transgene expression and assessed the antitumor activity and safety of Ad-TK-122T.
resultsInsertion of miR-122T specifically down-regulated transgene expression in vitro and selectively protected the miR-122-positive cells from killing by TK/GCV treatment. Insertion of miR-122T led to significant reduction of tansgene expression in the liver without inhibition of its expression in tumors in vivo, resulting in an 11-fold improvement of tumor-specific transgene expression. Intratumoral injection of Ad vectors mediated TK/GCV system led to a vector dosage-dependent regression of tumor. The insertion of miR-122T does not influence the antitumor effects of suicide gene therapy. Whereas mice administrated with Ad-TK showed severe lethal hepatotoxicity at the effective therapeutic dose, no liver damage was found in Ad-TK-122T group.
conclusionsmiR-122-regulated TK expression achieved effective anti-tumor effects and increased the safety of intratumoral delivery of adenovirus-mediated TK/GCV gene therapy for miR-122-deficient HCC.
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