ArticleNature communications2025
AAV vectors trigger DNA damage response-dependent pro-inflammatory signalling in human iPSC-derived CNS models and mouse brain.
Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed.
- Host Endoplasmic Reticulum Stress and Interferon Responses Contribute to AAV-Induced Ocular Toxicity.bioRxiv : the preprint server for biology · 2026Article
- A PepFect14 analog improves non-viral CRISPR delivery in primary human cells to facilitate genome editing and repair.Bioengineering & translational medicine · 2026Article
- Nanoparticle-assisted gene editing for genomic disorders in the central nervous system.Neural regeneration research · 2026Article
- AAV Vectors in Regenerative Medicine and Cellular Reprogramming: Potential, Pitfalls, and Specificity Constraints.International journal of molecular sciences · 2026Review
- ADAR-mediated RNA editing in CNS disorders: from pathogenic mechanisms to therapeutic opportunities.Cellular & molecular biology letters · 2026Review
- AAV-mediated GPR173 gene therapy attenuates long-term refractory epilepsy by enhancing synaptic GABAActa pharmacologica Sinica · 2026Article
- Attenuating AAV-triggered innate immunity in the adult mouse nervous systemActa pharmaceutica Sinica. B · 2026Article
- AAV NRF2 gene therapy preserves retinal structure and function in rodent models of oxidative damage.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Adeno-Associated Virus Vector Mediated Gene Therapy: A Promising Approach to Transform Hypertrophic Cardiomyopathy Treatment.Biotechnology journal · 2026Review
- Peripheral neuron phenotypes of familial dysautonomia are rescued by AAV-mediated gene therapy.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2026Article
- Immune response to adeno-associated viral vectors in a human iPSC-derived microglia chimeric mouse model.Cell reports methods · 2026Article
- DNA damage/p53, innate immune, and unfolded protein responses are activated in primate liver after toxic, high-dose AAV-SMN1 delivery.Molecular therapy. Advances · 2026Article
- Serotype-specific tropism of adeno-associated viruses in dorsal meningeal lymphatic vessels via intra-cisterna magna delivery.Frontiers in immunology · 2026Article
- The delivery challenge of adeno-associated virus vector-based gene therapies for neurological diseases.Frontiers in neuroscience · 2026Review
- Intravitreal AAV vector delivery induces integrin-dependent ocular inflammation, complement activation, and antiviral and DNA damage responses.Frontiers in immunology · 2026Article
- Compact Calm1 promoter enables AAV mediated neuron-targeted expression in human iPSC-derived brain organoids.Scientific reports · 2025Article
- Adeno-associated virus serotype 9 structural heterogeneity and stability characterized by charge detection mass spectrometry.Molecular therapy. Methods & clinical development · 2025Article
- An AAV-Based Therapy Approach for Neurological Phenotypes of X-Linked Adrenoleukodystrophy.International journal of molecular sciences · 2025Review
- Treating Hearing Loss: From Cochlear Implantation to Gene Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Cerebrovascular p16Acta neuropathologica communications · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors.
Funding
Abstract
Adeno-associated viral (AAV) vector-based gene therapy is gaining foothold as treatment for genetic neurological diseases with encouraging clinical results. Nonetheless, dose-dependent adverse events have emerged in recent clinical trials through mechanisms that remain unclear. We have modelled here the impact of AAV transduction in cell models of the human central nervous system (CNS), taking advantage of induced pluripotent stem cells. Our work uncovers vector-induced innate immune mechanisms that contribute to cell death. While empty AAV capsids were well tolerated, the AAV genome triggered p53-dependent DNA damage responses across CNS cell types followed by the induction of inflammatory responses. In addition, transgene expression led to MAVS-dependent activation of type I interferon responses. Formation of DNA damage foci in neurons and gliosis were confirmed in murine striatum upon intraparenchymal AAV injection. Transduction-induced cell death and gliosis could be prevented by inhibiting p53 or by acting downstream on STING- or IL-1R-mediated responses. Together, our work identifies innate immune mechanisms of vector sensing in the CNS that can potentially contribute to AAV-associated neurotoxicity.
Indexed as
Identifiers
What OpenQuestion holds
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.