ReviewFrontiers in immunology2014
Pre-Clinical Assessment of Immune Responses to Adeno-Associated Virus (AAV) Vectors.
Review in Frontiers in immunology, 2014. 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, 37 citations in OpenAlex.
- Nanoparticles targeting liver sinusoidal endothelial cells improve tolerance to vector and transgene antigens through tolerance spreading.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Low cross reactivity between wild type and deamidated AAV can lead to false negative results in immune monitoring T-cell assays.Frontiers in immunology · 2023Article
- Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper.Molecular therapy. Methods & clinical development · 2022Review
- Prenatal Somatic Cell Gene Therapies: Charting a Path Toward Clinical Applications (Proceedings of the CERSI-FDA Meeting).Journal of clinical pharmacology · 2022Review
- A narrative review of in utero gene therapy: advances, challenges, and future considerations.Translational pediatrics · 2021Review
- Adeno-Associated Viruses (AAV) and Host Immunity - A Race Between the Hare and the Hedgehog.Frontiers in immunology · 2021Review
- Immune-orthogonal orthologues of AAV capsids and of Cas9 circumvent the immune response to the administration of gene therapy.Nature biomedical engineering · 2019Article
- Systemic AAV Micro-dystrophin Gene Therapy for Duchenne Muscular Dystrophy.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Review
- RNA-Seq Analysis of an Antisense Sequence Optimized for Exon Skipping in Duchenne Patients Reveals No Off-Target Effect.Molecular therapy. Nucleic acids · 2018Article
- Adeno-Associated Virus Gene Therapy for Liver Disease.Human gene therapy · 2016Review
- Deimmunization for gene therapy: host matching of synthetic zinc finger constructs enables long-term mutant Huntingtin repression in mice.Molecular neurodegeneration · 2016Article
- Efficacy and safety of myocardial gene transfer of adenovirus, adeno-associated virus and lentivirus vectors in the mouse heart.Gene therapy · 2016Article
- Copackaged AAV9 Vectors Promote Simultaneous Immune Tolerance and Phenotypic Correction of Pompe Disease.Human gene therapy · 2016Article
- Gene Therapy for the Treatment of Neurological Disorders: Metabolic Disorders.Methods in molecular biology (Clifton, N.J.) · 2016Review
- Targeted approaches to induce immune tolerance for Pompe disease therapy.Molecular therapy. Methods & clinical development · 2016Review
- Article
- Strategies to circumvent humoral immunity to adeno-associated viral vectors.Expert opinion on biological therapy · 2015Review
- Optical stimulation for restoration of motor function after spinal cord injury.Mayo Clinic proceedings · 2015Review
- Adeno-Associated Viral Vectors at the Frontier between Tolerance and Immunity.Frontiers in immunology · 2015Article
- Gene therapy for the nervous system: challenges and new strategies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2014Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transitioning to human trials from pre-clinical models resulted in the emergence of inhibitory AAV vector immune responses which has become a hurdle for sustained correction. Early animal studies did not predict the full range of host immunity to the AAV vector in human studies. While pre-existing antibody titers against AAV vectors has been a lingering concern, cytotoxic T-cell (CTL) responses against the input capsid can prevent long-term therapy in humans. These discoveries spawned more thorough profiling of immune response to rAAV in pre-clinical models, which have assessed both innate and adaptive immunity and explored methods for bypassing these responses. Many efforts toward measuring innate immunity have utilized Toll-like receptor deficient models and have focused on differential responses to viral capsid and genome. From adaptive studies, it is clear that humoral responses are relevant for initial vector transduction efficiency while cellular responses impact long-term outcomes of gene transfer. Measuring humoral responses to AAV vectors has utilized in vitro neutralizing antibody assays and transfer of seropositive serum to immunodeficient mice. Overcoming antibodies using CD20 inhibitors, plasmapheresis, altering route of delivery and using different capsids have been explored. CTL responses were measured using in vitro and in vivo models. In in vitro assays expansion of antigen-specific T-cells as well as cytotoxicity toward AAV transduced cells can be shown. Many groups have successfully mimicked antigen-specific T-cell proliferation, but actual transgene level reduction and parameters of cytotoxicity toward transduced target cells have only been shown in one model. The model utilized adoptive transfer of capsid-specific in vitro expanded T-cells isolated from immunized mice with LPS as an adjuvant. Finally, the development of immune tolerance to AAV vectors by enriching regulatory T-cells as well as modulating the response pharmacologically has also been explored.
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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.