ArticleScientific reports2018
Synergistic and independent action of endogenous microRNAs 122a and 199a for post-transcriptional liver detargeting of gene vectors.
Article in Scientific reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 14 citations in OpenAlex.
- Gene Therapy Strategies for Uveal Melanoma: Adeno-associated Virus Delivery Challenges and Translational Opportunities.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- The aging choroid plexus and its relationship with gut dysbiosis and Klotho decline: possible intervention strategies.GeroScience · 2025Review
- Revolution of AAV in Drug Discovery: From Delivery System to Clinical Application.Journal of medical virology · 2025Review
- In vivo selection in non-human primates identifies AAV capsids for on-target CSF delivery to spinal cord.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Vector Affinity and Receptor Distribution Define Tissue-Specific Targeting in an Engineered AAV Capsid.Journal of virology · 2023Article
- MicroRNAs in cancer metastasis: biological and therapeutic implications.Expert reviews in molecular medicine · 2023Review
- Gene-based therapeutics for rare genetic neurodevelopmental psychiatric disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Hepatocellular Carcinoma Is a Natural Target for Adeno-Associated Virus (AAV) 2 Vectors.Cancers · 2022Article
- Synthetic Biology: Emerging Concepts to Design and Advance Adeno-Associated Viral Vectors for Gene Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Overcoming innate immune barriers that impede AAV gene therapy vectors.The Journal of clinical investigation · 2021Review
- Novel Combinatorial MicroRNA-Binding Sites in AAV Vectors Synergistically Diminish Antigen Presentation and Transgene Immunity for Efficient and Stable Transduction.Frontiers in immunology · 2021Article
- Variability in Cardiac miRNA-122 Level Determines Therapeutic Potential of miRNA-Regulated AAV Vectors.Molecular therapy. Methods & clinical development · 2020Article
- Transcriptional Targeting and MicroRNA Regulation of Lentiviral Vectors.Molecular therapy. Methods & clinical development · 2019Review
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
In hepatocellular carcinoma (HCC), which usually develops in a cirrhotic liver, treatments preserving normal liver function and viability are vitally important. Here, we utilise the differential expression of miRNAs 122a and 199a between normal hepatocytes and HCC to generate vectors harbouring their binding sites for hepatocyte detargeting. Using a reporter gene, we observed a synergistic detargeting of cells expressing both miRNAs as well as cells expressing either of the miRNAs; while expression was retained in HCC cells negative for both miRNA122a and miRNA199a. Mimics and inhibitors for individual miRNAs were used to confirm these results. Furthermore, suicide gene therapy with cytosine deaminase (CD)/5-fluorocytosine system resulted in limited killing of cells expressing either of the two miRNAs. Finally, we report feasibility of using adeno associated virus (AAV) based vectors for delivery of this dual regulated gene delivery system. These results present a novel dual targeted system whereby miRNA122a and miRNA199a act either synergistically or independently in regulating transgene expression with vectors harbouring binding sites of both miRNAs and have implications in detargeting vectors from multiple cell types in the liver.
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