ArticlePloS one2014
Transgene regulation using the tetracycline-inducible TetR-KRAB system after AAV-mediated gene transfer in rodents and nonhuman primates.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- Engineering Protein Stability with Small Molecules: A Review of the ecDHFR Destabilizing Domain System.ACS chemical biology · 2026Review
- Regulatable In Vivo Gene Expression via Adaptamers.bioRxiv : the preprint server for biology · 2025Article
- Immune-driven gene expression loss following intramuscular AAV delivery to non-human primates is only transient.Molecular therapy. Methods & clinical development · 2025Article
- Review
- miR-122/PPARβ axis is involved in hypoxic exercise and modulates fatty acid metabolism in skeletal muscle of obese rats.Heliyon · 2024Article
- PK/PD and Bioanalytical Considerations of AAV-Based Gene Therapies: an IQ Consortium Industry Position Paper.The AAPS journal · 2023Review
- Lentiviral vectors for inducible, transactivator-free advanced therapy medicinal products: Application to CAR-T cells.Molecular therapy. Nucleic acids · 2023Article
- Gene Therapy for Regenerative Medicine.Pharmaceutics · 2023Review
- RuX: A Novel, Flexible, and Sensitive Mifepristone-Induced Transcriptional Regulation System.International journal of cell biology · 2023Article
- Outer retinal transduction by AAV2-7m8 following intravitreal injection in a sheep model of CNGA3 achromatopsia.Gene therapy · 2022Article
- Optimized riboswitch-regulated AAV vector for VEGF-B gene therapy.Frontiers in medicine · 2022Article
- Optimized pharmacological control over the AAV-Gene-Switch vector for regulable gene therapy.Molecular therapy. Methods & clinical development · 2021Article
- Uncoupling proteins in the mitochondrial defense against oxidative stress.Progress in retinal and eye research · 2021Review
- Synthetic Biology: Emerging Concepts to Design and Advance Adeno-Associated Viral Vectors for Gene Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Gene-Based Therapeutics for Acquired Retinal Disease: Opportunities and Progress.Frontiers in genetics · 2021Review
- Adipose Tissue: An Emerging Target for Adeno-associated Viral Vectors.Molecular therapy. Methods & clinical development · 2020Review
- Retinal Tropism and Transduction of Adeno-Associated Virus Varies by Serotype and Route of Delivery (Intravitreal, Subretinal, or Suprachoroidal) in Rats.Human gene therapy · 2020Article
- GDNF Gene Therapy to Repair the Injured Peripheral Nerve.Frontiers in bioengineering and biotechnology · 2020Review
- Externally-Controlled Systems for Immunotherapy: From Bench to Bedside.Frontiers in immunology · 2020Review
- Development of a forward-oriented therapeutic lentiviral vector for hemoglobin disorders.Nature communications · 2019Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Numerous studies have demonstrated the efficacy of the Adeno-Associated Virus (AAV)-based gene delivery platform in vivo. The control of transgene expression in many protocols is highly desirable for therapeutic applications and/or safety reasons. To date, the tetracycline and the rapamycin dependent regulatory systems have been the most widely evaluated. While the long-term regulation of the transgene has been obtained in rodent models, the translation of these studies to larger animals, especially to nonhuman primates (NHP), has often resulted in an immune response against the recombinant regulator protein involved in transgene expression regulation. These immune responses were dependent on the target tissue and vector delivery route. Here, using AAV vectors, we evaluated a doxycyclin-inducible system in rodents and macaques in which the TetR protein is fused to the human Krüppel associated box (KRAB) protein. We demonstrated long term gene regulation efficiency in rodents after subretinal and intramuscular administration of AAV5 and AAV1 vectors, respectively. However, as previously described for other chimeric transactivators, the TetR-KRAB-based system failed to achieve long term regulation in the macaque after intramuscular vector delivery because of the development of an immune response. Thus, immunity against the chimeric transactivator TetR-KRAB emerged as the primary limitation for the clinical translation of the system when targeting the skeletal muscle, as previously described for other regulatory proteins. New developments in the field of chimeric drug-sensitive transactivators with the potential to not trigger the host immune system are still needed.
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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.