ArticlePloS one2018
Sustained AAV9-mediated expression of a non-self protein in the CNS of non-human primates after immunomodulation.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Differential expression of monoclonal antibody in rat brain following systemic and local administration of AAV.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Immune response to adeno-associated viral vectors in a human iPSC-derived microglia chimeric mouse model.Cell reports methods · 2026Article
- A dose escalation and safety study of AAVrh10-mediated Schwann cell-targeted gene therapy for CMT1X.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Comparative assessment of the transduction efficiency and safety associated with the delivery of AAV9-GFP vector via lumbar puncture to cynomolgus macaques with and without anti-AAV9 pre-existing antibodies.Molecular therapy. Methods & clinical development · 2024Article
- AAV-based in vivo gene therapy for neurological disorders.Nature reviews. Drug discovery · 2023Review
- Tolerability and tropism of recombinant adeno-associated virus vectors in the African green monkey (Chlorocebus sabaeus) anterior chamber.Gene therapy · 2023Article
- Assessment of AAV9 distribution and transduction in rats after administration through Intrastriatal, Intracisterna magna and Lumbar Intrathecal routes.Gene therapy · 2023Article
- Red Blood Cell Anchoring Enables Targeted Transduction and Re-Administration of AAV-Mediated Gene Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Single-Dose Intrathecal Dorsal Root Ganglia Toxicity of Onasemnogene Abeparvovec in Cynomolgus Monkeys.Human gene therapy · 2022Article
- Intrathecal sc-AAV9-CB-GFP: Systemic Distribution Predominates Following Single-Dose Administration in Cynomolgus Macaques.Toxicologic pathology · 2022Article
- Characterization of AAV-mediated dorsal root ganglionopathy.Molecular therapy. Methods & clinical development · 2022Article
- Efficacy of AAV serotypes to target Schwann cells after intrathecal and intravenous delivery.Scientific reports · 2021Article
- AAV9-mediated Schwann cell-targeted gene therapy rescues a model of demyelinating neuropathy.Gene therapy · 2021Article
- Investigating Immune Responses to the scAAV9-International journal of molecular sciences · 2021Article
- Gene Transfer in Adeno-Associated Virus Seropositive Rhesus Macaques Following Rapamycin Treatment and Subcutaneous Delivery of AAV6, but Not Retargeted AAV6 Vectors.Human gene therapy · 2021Article
- Preclinical testing of AAV9-PHP.B for transgene expression in the non-human primate cochlea.Hearing research · 2020Article
- Correction: Sustained AAV9-mediated expression of a non-self protein in the CNS of non-human primates after immunomodulation.PloS one · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
A critical issue in transgene delivery studies is immune reactivity to the transgene- encoded protein and its impact on sustained gene expression. Here, we test the hypothesis that immunomodulation by rapamycin can decrease immune reactivity after intrathecal AAV9 delivery of a transgene (GFP) in non-human primates, resulting in sustained GFP expression in the CNS. We show that rapamycin treatment clearly reduced the overall immunogenicity of the AAV9/GFP vector by lowering GFP- and AAV9-specific antibody responses, and decreasing T cell responses including cytokine and cytolytic effector responses. Spinal cord GFP protein expression was sustained for twelve weeks, with no toxicity. Immune correlates of robust transgene expression include negligible GFP-specific CD4 and CD8 T cell responses, absence of GFP-specific IFN-γ producing T cells, and absence of GFP-specific cytotoxic T cells, which support the hypothesis that decreased T cell reactivity results in sustained transgene expression. These data strongly support the use of modest doses of rapamycin to modulate immune responses for intrathecal gene therapies, and potentially a much wider range of viral vector-based therapeutics.
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Registered trials
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.