ArticlePloS one2011
Viral single-strand DNA induces p53-dependent apoptosis in human embryonic stem cells.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed.
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- AAV transduction of human glioblastoma cell lines induces perturbation in cell proliferation.Molecular therapy. Oncology · 2026Article
- ATM Inhibition Enhances Knock-in Efficiency by Suppressing AAV-Induced Activation of Apoptotic Pathways.Communications biology · 2026Article
- AAV Kills Dividing Cells by Depleting PARP1 and Other DNA Damage Response Proteins.bioRxiv : the preprint server for biology · 2025Article
- Allele-specific depletion ofMolecular therapy. Oncology · 2025Article
- Adeno-Associated Virus 2 (AAV2) - Induced RPA exhaustion generates cellular DNA damage and restricts viral gene expression.PLoS pathogens · 2025Article
- Unveiling Small Non-Coding RNA Dynamics During Recombinant Adeno-Associated Virus Production.Biotechnology journal · 2025Article
- AAV vector development, back to the future.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- AAV vectors trigger DNA damage response-dependent pro-inflammatory signalling in human iPSC-derived CNS models and mouse brain.Nature communications · 2025Article
- Review
- AAV vector transduction restriction and attenuated toxicity in hESCs via a rationally designed inverted terminal repeat.Nucleic acids research · 2025Article
- AAV2 can replicate its DNA by a rolling hairpin or rolling circle mechanism, depending on the helper virus.Journal of virology · 2024Article
- Transient inhibition of 53BP1 increases the frequency of targeted integration in human hematopoietic stem and progenitor cells.Nature communications · 2024Article
- Analyzing efficacy, stability, and safety of AAV-mediated optogenetic hearing restoration in mice.Life science alliance · 2022Article
- Transduction of rat and human adipose-tissue derived mesenchymal stromal cells by adeno-associated viral vector serotype DJ.Biology open · 2021Article
- Tissue and cell-type-specific transduction using rAAV vectors in lung diseases.Journal of molecular medicine (Berlin, Germany) · 2021Review
- Article
- Harnessing the Natural Biology of Adeno-Associated Virus to Enhance the Efficacy of Cancer Gene Therapy.Viruses · 2021Review
- Answered and Unanswered Questions in Early-Stage Viral Vector Transduction Biology and Innate Primary Cell Toxicity forFrontiers in immunology · 2021Review
- Adeno-Associated Virus Vector Mobilization, Risk Versus Reality.Human gene therapy · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
Abstract
Human embryonic stem cells (hESCs) are primed for rapid apoptosis following mild forms of genotoxic stress. A natural form of such cellular stress occurs in response to recombinant adeno-associated virus (rAAV) single-strand DNA genomes, which exploit the host DNA damage response for replication and genome persistence. Herein, we discovered a unique DNA damage response induced by rAAV transduction specific to pluripotent hESCs. Within hours following rAAV transduction, host DNA damage signaling was elicited as measured by increased gamma-H2AX, ser15-p53 phosphorylation, and subsequent p53-dependent transcriptional activation. Nucleotide incorporation assays demonstrated that rAAV transduced cells accumulated in early S-phase followed by the induction of apoptosis. This lethal signaling sequalae required p53 in a manner independent of transcriptional induction of Puma, Bax and Bcl-2 and was not evident in cells differentiated towards a neural lineage. Consistent with a lethal DNA damage response induced upon rAAV transduction of hESCs, empty AAV protein capsids demonstrated no toxicity. In contrast, DNA microinjections demonstrated that the minimal AAV origin of replication and, in particular, a 40 nucleotide G-rich tetrad repeat sequence, was sufficient for hESC apoptosis. Our data support a model in which rAAV transduction of hESCs induces a p53-dependent lethal response that is elicited by a telomeric sequence within the AAV origin of replication.
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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.