ArticleJournal of virology2002
Lack of an immune response against the tetracycline-dependent transactivator correlates with long-term doxycycline-regulated transgene expression in nonhuman primates after intramuscular injection of recombinant adeno-associated virus.
Article in Journal of virology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 147 citations in OpenAlex.
- Regulatable in vivo gene expression via adaptamers.Molecular cell · 2026Article
- Tunable gene control via RNA splicing with a clinically approved small molecule.Nature communications · 2026Article
- Assessment of Immune Responses Against AAV Encoded Transgene Products.The AAPS journal · 2026Review
- Regulatable In Vivo Gene Expression via Adaptamers.bioRxiv : the preprint server for biology · 2025Article
- ADARs: pleiotropy in function, versatility in application.Nucleic acids research · 2025Review
- Claudin-6 mediates an embryonic stem cell-driven antitumor response against breast cancer.iScience · 2025Article
- Immune-driven gene expression loss following intramuscular AAV delivery to non-human primates is only transient.Molecular therapy. Methods & clinical development · 2025Article
- A peptide conjugate enables systemic injection of the morpholino inducer and more durable induction of T3H38 ribozyme-controlled AAV transgene in mice.Gene therapy · 2025Article
- Review
- Adeno-associated virus vectors and neurotoxicity-lessons from preclinical and human studies.Gene therapy · 2025Review
- Next-generation strategies to improve safety and efficacy of adeno-associated virus-based gene therapy for hemophilia: lessons from clinical trials in other gene therapies.Haematologica · 2024Review
- Control of mammalian gene expression by modulation of polyA signal cleavage at 5' UTR.Nature biotechnology · 2024Article
- Ligify: Automated Genome Mining for Ligand-Inducible Transcription Factors.ACS synthetic biology · 2024Article
- Adeno-associated virus as a delivery vector for gene therapy of human diseases.Signal transduction and targeted therapy · 2024Review
- Oxidative stress induced by sustained supraphysiological intrastriatal GDNF delivery is prevented by dose regulation.Molecular therapy. Methods & clinical development · 2023Article
- Multidimensional control of therapeutic human cell function with synthetic gene circuits.Science (New York, N.Y.) · 2022Article
- AAV Vector-Mediated Antibody Delivery (A-MAD) in the Central Nervous System.Frontiers in neurology · 2022Review
- Optimized pharmacological control over the AAV-Gene-Switch vector for regulable gene therapy.Molecular therapy. Methods & clinical development · 2021Article
- 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
10 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We previously documented persistent regulation of erythropoietin (Epo) secretion in mice after a single intramuscular (i.m.) injection of a recombinant adeno-associated virus (rAAV) vector harboring both the tetracycline-dependent transactivator (rtTA) and the Epo cDNA (D. Bohl, A. Salvetti, P. Moullier, and J. M. Heard, Blood 92:1512-1517, 1998). Using the same vector harboring the cynomolgus macaque Epo cDNA instead, the present study evaluated the ability of the tetracycline-regulatable (tetR) system to establish long-term transgene regulation in nonhuman primates. The vector was administered i.m., after which 5-day induction pulses were performed monthly for up to 13 months by using doxycycline (DOX), a tetracycline analog. We show that initial inductions were successful in all individuals and that there was a tight regulation and a rapid deinduction pattern upon DOX withdrawal. For one macaque, regulation of Epo secretion was maintained during the entire experimental period; for the five remaining macaques, secreted Epo became indistinguishable from endogenous Epo upon repeated DOX inductions. We investigated the mechanism involved and showed that, except in the animal in which secretion persisted, delayed humoral and cellular immune responses were directed against the rtTA transactivator protein associated with the reduction of vector DNA in transduced muscles. This study provides some evidence that, when the immune system is not mobilized against the rtTA transactivator, the tetR-regulatable system is able to support long-term transgene regulation in the context of an rAAV in nonhuman primates. In addition, our results suggest potential improvements for vector design.
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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.