ReviewHuman gene therapy2025
Pre-Existing Anti-Adeno-Associated Virus Immunity in Gene Therapy: Mechanisms, Challenges, and Potential Solutions.
Review in Human gene therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 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
4 citing papers in PubMed.
- Preclinical efficacy of a gene therapy forMolecular therapy. Advances · 2026Article
- Environmental and developmental factors shape anti-AAV immunity in pigs.Gene therapy · 2026Article
- Immune Response Associated Hepatotoxicity in Hemophilia Gene Therapy: Mechanisms, Management, and Challenges.Journal of hematology · 2026Review
- Should patients with pre-existing anti-AAV antibodies be excluded from receiving intrathecally delivered AAV vectors?Molecular therapy. Methods & clinical development · 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
4 authors.
Funding
Abstract
Adeno-associated virus (AAV) vectors have emerged as versatile and promising tools in gene therapy due to their favorable safety profile, broad tissue tropism, and long-term gene expression. However, pre-existing immunity, especially in the form of neutralizing antibodies (NAbs) remains a significant barrier, reducing vector efficacy and restricting patient eligibility. This review provides a comprehensive overview of the immunological landscape affecting AAV gene therapy, including global seroprevalence, environmental influences, and antibody cross-reactivity stemming from natural parvovirus exposure or vaccination of animal research models.We detail the mechanisms underlying immune detection and vector clearance, covering innate pattern recognition receptors, complement activation, and adaptive immune effector functions such as antibody-dependent complement deposition, cytotoxicity, and phagocytosis.We further analyze how species, age, serotype, administration route, and target tissue contribute to immune susceptibility and variable transduction outcomes. To overcome these challenges, we propose a three-pronged classification of mitigation strategies: (1) immune-focused strategies, such as plasmapheresis, immunoadsorption, enzymatic antibody cleavage, corticosteroids, and B cell depletion; (2) delivery-focused strategies, which include targeting immune-privileged sites, localized or intrathecal delivery, and timing of vector administration; and (3) capsid-focused strategies, comprising rational capsid engineering and the use of decoy particles or empty capsids.We also discuss promising advances such as AAV-specific regulatory T cells and re-dosable AAV platforms. This strategic framework offers a roadmap for tailoring gene therapy approaches to individual immune profiles and improving the safety, efficacy, and accessibility of AAVbased therapeutics.
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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.