ArticleeLife2021
AAV ablates neurogenesis in the adult murine hippocampus.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 86 citations in OpenAlex.
- Adeno-associated virus-induced neurotoxicity is prevented by CpG depletion.Molecular therapy. Advances · 2026Article
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- Astrocytic Igfbp2 Promotes Spontaneous Seizures in a Mouse Model of Mesial Temporal Lobe Epilepsy.Glia · 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
- Open-source, high performance miniature 2-photon microscopy systems for freely behaving animals.Nature communications · 2025Article
- Characterization of a novel transgenic mouse model to investigate brain-wide activation of astrocyte Gq signaling.Lab animal · 2025Article
- Functional Maturation and Experience-Dependent Plasticity in Adult-Born Olfactory Bulb Dopaminergic Neurons.The European journal of neuroscience · 2025Article
- AAV vector development, back to the future.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- The role of electroencephalography in epilepsy research-From seizures to interictal activity and comorbidities.Epilepsia · 2025Review
- AAV vector transduction restriction and attenuated toxicity in hESCs via a rationally designed inverted terminal repeat.Nucleic acids research · 2025Article
- Adeno-associated virus vectors and neurotoxicity-lessons from preclinical and human studies.Gene therapy · 2025Review
- Focused Ultrasounds as an Adeno-Associated Virus Gene Therapy-Empowering Tool in Juvenile Mice via Intracerebroventricular Administration.Human gene therapy · 2024Article
- PTEN deletion in the adult dentate gyrus induces epilepsy.Neurobiology of disease · 2024Article
- AAV vector-derived elements integrate into Cas9-generated double-strand breaks and disrupt gene transcription.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- PTEN DELETION IN THE ADULT DENTATE GYRUS INDUCES EPILEPSY.bioRxiv : the preprint server for biology · 2024Article
- Adult neurogenesis improves spatial information encoding in the mouse hippocampus.Nature communications · 2024Article
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- An innate immune response to adeno-associated virus genomes decreases cortical dendritic complexity and disrupts synaptic transmission.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Recombinant adeno-associated virus (rAAV) has been widely used as a viral vector across mammalian biology and has been shown to be safe and effective in human gene therapy. We demonstrate that neural progenitor cells (NPCs) and immature dentate granule cells (DGCs) within the adult murine hippocampus are particularly sensitive to rAAV-induced cell death. Cell loss is dose dependent and nearly complete at experimentally relevant viral titers. rAAV-induced cell death is rapid and persistent, with loss of BrdU-labeled cells within 18 hr post-injection and no evidence of recovery of adult neurogenesis at 3 months post-injection. The remaining mature DGCs appear hyperactive 4 weeks post-injection based on immediate early gene expression, consistent with previous studies investigating the effects of attenuating adult neurogenesis. In vitro application of AAV or electroporation of AAV2 inverted terminal repeats (ITRs) is sufficient to induce cell death. Efficient transduction of the dentategyrus (DG)- without ablating adult neurogenesis- can be achieved by injection of rAAV2-retro serotyped virus into CA3. rAAV2-retro results in efficient retrograde labeling of mature DGCs and permits in vivo two-photon calcium imaging of dentate activity while leaving adult neurogenesis intact. These findings expand on recent reports implicating rAAV-linked toxicity in stem cells and other cell types and suggest that future work using rAAV as an experimental tool in the DG and as a gene therapy for diseases of the central nervous system should be carefully evaluated.
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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.