ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
miR-148a- and miR-216a-regulated oncolytic adenoviruses targeting pancreatic tumors attenuate tissue damage without perturbation of miRNA activity.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 36 citations in OpenAlex.
- RNA Therapeutics: Delivery Problems and Solutions-A Review.Pharmaceutics · 2025Review
- Immune Checkpoint Inhibitors Combined with Oncolytic Virotherapy: Synergy, Heterogeneity, and Safety in Cancer Treatment.Oncology research · 2025Review
- miRNA-Mediated Mechanisms in the Generation of Effective and Safe Oncolytic Viruses.Pharmaceutics · 2024Review
- MicroRNAs: emerging biomarkers and therapeutic targets in pancreatic cancer.Frontiers in molecular biosciences · 2024Review
- MicroRNA-216a is essential for cardiac angiogenesis.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- The role of viruses in cancer development versus cancer therapy: An oncological perspective.Cancer medicine · 2023Review
- MicroRNAs in cancer metastasis: biological and therapeutic implications.Expert reviews in molecular medicine · 2023Review
- miRNA Pathway Alteration in Response to Non-Coding RNA Delivery in Viral Vector-Based Gene Therapy.International journal of molecular sciences · 2022Review
- Bovine Milk-Derived Extracellular Vesicles Inhibit Catabolic and Inflammatory Processes in Cartilage from Osteoarthritis Patients.Molecular nutrition & food research · 2022Article
- An Extensive Review on Preclinical and Clinical Trials of Oncolytic Viruses Therapy for Pancreatic Cancer.Frontiers in oncology · 2022Review
- MicroRNA-detargeting proves more effective thanMolecular therapy oncolytics · 2021Article
- Article
- Oncolytic Viruses in Combination Therapeutic Approaches with Epigenetic Modulators: Past, Present, and Future Perspectives.Cancers · 2021Review
- Review
- Extremely Low Organ Toxicity and Strong Antitumor Activity of miR-34-Regulated Oncolytic Coxsackievirus B3.Molecular therapy oncolytics · 2019Article
- Review
- MicroRNA-Regulated Gene Delivery Systems for Research and Therapeutic Purposes.Molecules (Basel, Switzerland) · 2018Review
- Article
- Effect of young exosomes injected in aged mice.International journal of nanomedicine · 2018Article
- Translational reprogramming in tumour cells can generate oncoselectivity in viral therapies.Nature communications · 2017Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oncolytic virotherapy shows promise for pancreatic ductal adenocarcinoma (PDAC) treatment, but there is the need to minimize associated-toxicities. In the current work, we engineered artificial target sites recognized by miR-216a and/or miR-148a to provide pancreatic tumor-selectivity to replication-competent adenoviruses (Ad-miRTs) and improve their safety profile. Expression analysis in PDAC patients identified miR-148a and miR-216a downregulated in resectable (FC(miR-148a) = 0.044, P < 0.05; FC(miR-216a) = 0.017, P < 0.05), locally advanced (FC(miR-148a) = 0.038, P < 0.001; FC(miR-216a) = 0.001, P < 0.001) and metastatic tumors (FC(miR-148a) = 0.041, P < 0.01; FC(miR-216a) = 0.002, P < 0.001). In mouse tissues, miR-216a was highly specific of the exocrine pancreas whereas miR-148a was abundant in the exocrine pancreas, Langerhans islets, and the liver. In line with the miRNA content and the miRNA target site design, we show E1A gene expression and viral propagation efficiently controlled in Ad-miRT-infected cells. Consequently, Ad-miRT-infected mice presented reduced pancreatic and liver damage without perturbation of the endogenous miRNAs and their targets. Interestingly, the 8-miR148aT design showed repressing activity by all miR-148/152 family members with significant detargeting effects in the pancreas and liver. Ad-miRTs preserved their oncolytic activity and triggered strong antitumoral responses. This study provides preclinical evidences of miR-148a and miR-216a target site insertions to confer adenoviral selectivity and proposes 8-miR148aT as an optimal detargeting strategy for genetically-engineered therapies against PDAC.
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