ArticleMolecular therapy : the journal of the American Society of Gene Therapy2012
Gene transfer to the CNS is efficacious in immune-primed mice harboring physiologically relevant titers of anti-AAV antibodies.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 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
25 citing papers in PubMed, 30 citations in OpenAlex.
- Pharmacodynamics, Efficacy, and Safety of Intraputaminal Eladocagene Exuparvovec Administered to Pediatric Patients With Aromatic L-Amino Acid Decarboxylase Deficiency Using an MR-Compatible Cannula: 48 Weeks of Follow-Up.Journal of inherited metabolic disease · 2026Trial
- ADAR-mediated RNA editing in CNS disorders: from pathogenic mechanisms to therapeutic opportunities.Cellular & molecular biology letters · 2026Review
- Use of CD19-targeted immune modulation to eradicate AAV-neutralizing antibodies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Redosing of AAV vectors in the brain after intracranial injections: Low-ish hanging fruit?Molecular therapy. Methods & clinical development · 2025Article
- Probing aspects of extracellular vesicle associated AAV allows increased vector yield and insight into its transduction and immune-evasive properties.Molecular therapy. Methods & clinical development · 2025Article
- Intracranial AAV administration dose-dependently recruits B cells to inhibit the AAV redosing.Molecular therapy. Methods & clinical development · 2025Article
- Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.Biomedicines · 2024Review
- Preexisting antibody assays for gene therapy: Considerations on patient selection cutoffs and companion diagnostic requirements.Molecular therapy. Methods & clinical development · 2024Review
- A versatile toolkit for overcoming AAV immunity.Frontiers in immunology · 2022Review
- Kinetics and durability of transgene expression after intrastriatal injection of AAV9 vectors.Frontiers in neurology · 2022Article
- Preclinical testing of AAV9-PHP.B for transgene expression in the non-human primate cochlea.Hearing research · 2020Article
- Adeno-Associated Virus Neutralizing Antibodies in Large Animals and Their Impact on Brain Intraparenchymal Gene Transfer.Molecular therapy. Methods & clinical development · 2018Article
- Rationally designed AAV2 and AAVrh8R capsids provide improved transduction in the retina and brain.Gene therapy · 2018Article
- Current and Future Treatments for Lysosomal Storage Disorders.Current treatment options in neurology · 2017Review
- AAV-mediated delivery of optogenetic constructs to the macaque brain triggers humoral immune responses.Journal of neurophysiology · 2017Article
- Adeno-Associated Virus-Based Gene Therapy for CNS Diseases.Human gene therapy · 2016Review
- rAAV Gene Therapy in a Canavan's Disease Mouse Model Reveals Immune Impairments and an Extended Pathology Beyond the Central Nervous System.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Strategies to circumvent humoral immunity to adeno-associated viral vectors.Expert opinion on biological therapy · 2015Review
- AAVrh.10 immunogenicity in mice and humans. Relevance of antibody cross-reactivity in human gene therapy.Gene therapy · 2015Article
- Recent advances in gene therapy for lysosomal storage disorders.The application of clinical genetics · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Central nervous system (CNS)-directed gene therapy with recombinant adeno-associated virus (AAV) vectors has been used effectively to slow disease course in mouse models of several neurodegenerative diseases. However, these vectors were typically tested in mice without prior exposure to the virus, an immunological scenario unlikely to be duplicated in human patients. Here, we examined the impact of pre-existing immunity on AAV-mediated gene delivery to the CNS of normal and diseased mice. Antibody levels in brain tissue were determined to be 0.6% of the levels found in systemic circulation. As expected, transgene expression in brains of mice with relatively high serum antibody titers was reduced by 59-95%. However, transduction activity was unaffected in mice that harbored more clinically relevant antibody levels. Moreover, we also showed that markers of neuroinflammation (GFAP, Iba1, and CD3) and histopathology (hematoxylin and eosin (H&E)) were not enhanced in immune-primed mice (regardless of pre-existing antibody levels). Importantly, we also demonstrated in a mouse model of Niemann Pick Type A (NPA) disease that pre-existing immunity did not preclude either gene transfer to the CNS or alleviation of disease-associated neuropathology. These findings support the continued development of AAV-based therapies for the treatment of neurological disorders.
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.