ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
Development of a liver-specific Tet-on inducible system for AAV vectors and its application in the treatment of liver cancer.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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36 citing papers in PubMed, 58 citations in OpenAlex.
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- Tumor-specific AAV delivery of interleukin-12 enhances antitumor immunity and safety in ovarian cancer xenograft mouse model.Molecular therapy. Oncology · 2025Article
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- Interleukin-12 Delivery Strategies and Advances in Tumor Immunotherapy.Current issues in molecular biology · 2024Review
- Recent advances of engineered oncolytic viruses-based combination therapy for liver cancer.Journal of translational medicine · 2024Review
- Riboswitch-controlled IL-12 gene therapy reduces hepatocellular cancer in mice.Frontiers in immunology · 2024Article
- Intratumoral immunotherapy with mRNAs encoding chimeric protein constructs encompassing IL-12, CD137 agonists, and TGF-β antagonists.Molecular therapy. Nucleic acids · 2023Article
- Systemic gene therapy with thymosin β4 alleviates glomerular injury in mice.Scientific reports · 2022Article
- Hepatocellular Carcinoma Is a Natural Target for Adeno-Associated Virus (AAV) 2 Vectors.Cancers · 2022Article
- A Small Virus to Deliver Small Antibodies: New Targeted Therapies Based on AAV Delivery of Nanobodies.Microorganisms · 2021Review
- Long-Term Systemic Expression of a Novel PD-1 Blocking Nanobody from an AAV Vector Provides Antitumor Activity without Toxicity.Biomedicines · 2020Article
- Short-Term Local Expression of a PD-L1 Blocking Antibody from a Self-Replicating RNA Vector Induces Potent Antitumor Responses.Molecular therapy : the journal of the American Society of Gene Therapy · 2019Article
- In-Depth Characterization of a Mifepristone-Regulated Expression System for AAV5-Mediated Gene Therapy in the Liver.Molecular therapy. Methods & clinical development · 2019Article
- Hippo-YAP/TAZ signalling in organ regeneration and regenerative medicine.Nature reviews. Molecular cell biology · 2019Review
- Liver-specific insulin receptor isoform A expression enhances hepatic glucose uptake and ameliorates liver steatosis in a mouse model of diet-induced obesity.Disease models & mechanisms · 2019Article
- Development of a liver-specific Tet-off AAV8 vector for improved safety of insulin gene therapy for diabetes.The journal of gene medicine · 2019Article
- Seek and destroy: targeted adeno-associated viruses for gene delivery to hepatocellular carcinoma.Drug delivery · 2017Review
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recombinant adeno-associated virus (rAAV) are effective gene delivery vehicles that can mediate long-lasting transgene expression. However, tight regulation and tissue-specific transgene expression is required for certain therapeutic applications. For regulatable expression from the liver we designed a hepatospecific bidirectional and autoregulatory tetracycline (Tet)-On system (Tet(bidir)Alb) flanked by AAV inverted terminal repeats (ITRs). We characterized the inducible hepatospecific system in comparison with an inducible ubiquitous expression system (Tet(bidir)CMV) using luciferase (luc). Although the ubiquitous system led to luc expression throughout the mouse, luc expression derived from the hepatospecific system was restricted to the liver. Interestingly, the induction rate of the Tet(bidir)Alb was significantly higher than that of Tet(bidir)CMV, whereas leakage of Tet(bidir)Alb was significantly lower. To evaluate the therapeutic potential of this vector, an AAV-Tet(bidir)-Alb-expressing interleukin-12 (IL-12) was tested in a murine model for hepatic colorectal metastasis. The vector induced dose-dependent levels of IL-12 and interferon-γ (IFN-γ), showing no significant toxicity. AAV-Tet(bidir)-Alb-IL-12 was highly efficient in preventing establishment of metastasis in the liver and induced an efficient T-cell memory response to tumor cells. Thus, we have demonstrated persistent, and inducible in vivo expression of a gene from a liver-specific Tet-On inducible construct delivered via an AAV vector and proved to be an efficient tool for treating liver cancer.
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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.