ArticleBlood advances2019
Immunoadsorption enables successful rAAV5-mediated repeated hepatic gene delivery in nonhuman primates.
Article in Blood advances, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 55 citations in OpenAlex.
- Rapamycin nanoparticles mitigate anti-AAV antibody formation in a mouse model of ornithine transcarbamylase deficiency.Molecular therapy. Advances · 2026Article
- Prevalence of pre-existing neutralizing antibodies to AAV5 and AAV8 in patients with Wilson's disease.Molecular therapy. Advances · 2026Article
- Novel AAV843 Vector-Mediated Gene Replacement Therapy Rescues Primary Hyperoxaluria Type I in Mice.Cells · 2026Article
- Immunogenicity of Gene and Cell Therapies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- From molecular correction to functional rescue: delivery, tissue state, and immunobiology as the principal constraints on dystrophin-restoring therapy in Duchenne muscular dystrophy.Frontiers in pharmacology · 2026Review
- Pre-Existing Anti-Adeno-Associated Virus Immunity in Gene Therapy: Mechanisms, Challenges, and Potential Solutions.Human gene therapy · 2025Review
- Emerging Technologies Tackling Adeno-Associated Viruses (AAV) Immunogenicity in Gene Therapy Applications.Pharmaceutics · 2025Review
- Enhancing gene transfer to renal tubules and podocytes by context-dependent selection of AAV capsids.Nature communications · 2024Article
- Insights in AAV-mediated antigen-specific immunity and a strategy for AAV vaccine dose reduction through AAV-extracellular vesicle association.Molecular therapy. Methods & clinical development · 2024Article
- In Vivo Selection of S/MAR Sequences to Favour AAV Episomal Maintenance in Dividing Cells.International journal of molecular sciences · 2024Article
- Enhanced AAV transduction across preclinical CNS models: A comparative study in human brain organoids with cross-species evaluations.Molecular therapy. Nucleic acids · 2024Article
- Hemophilia B and gene therapy: a new chapter with etranacogene dezaparvovec.Blood advances · 2024Review
- Harnessing whole human liver ex situ normothermic perfusion for preclinical AAV vector evaluation.Nature communications · 2024Article
- Liver directed adeno-associated viral vectors to treat metabolic disease.Journal of inherited metabolic disease · 2024Review
- Readministration of high-dose adeno-associated virus gene therapy vectors enabled by ImmTOR nanoparticles combined with B cell-targeted agents.PNAS nexus · 2023Article
- Rescue of infant progressive familial intrahepatic cholestasis type 3 mice by repeated dosing of AAV gene therapy.JHEP reports : innovation in hepatology · 2023Article
- Gene therapy for liver diseases - progress and challenges.Nature reviews. Gastroenterology & hepatology · 2023Review
- Assessment of Pre-Clinical Liver Models Based on Their Ability to Predict the Liver-Tropism of Adeno-Associated Virus Vectors.Human gene therapy · 2023Article
- Multiplexing AAV Serotype-Specific Neutralizing Antibodies in Preclinical Animal Models and Humans.Biomedicines · 2023Article
- Immune Responses to Gene Editing by Viral and Non-Viral Delivery Vectors Used in Retinal Gene Therapy.Pharmaceutics · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adeno-associated virus (AAV)-based liver gene therapy has been shown to be clinically successful. However, the presence of circulating neutralizing antibodies (NABs) against AAV vector capsids remains a major challenge as it may prevent successful transduction of the target cells. Therefore, there is a need to develop strategies that would enable AAV-mediated gene delivery to patients with preexisting anti-AAV NABs. In the current study, the feasibility of using an immunoadsorption (IA) procedure for repeated, liver-targeted gene delivery in nonhuman primates was explored. The animals were administered IV with recombinant AAV5 (rAAV5) carrying the reporter gene human secreted embryonic alkaline phosphatase (hSEAP). Seven weeks after the first rAAV treatment, all of the animals were readministered with rAAV5 carrying the therapeutic hemophilia B gene human factor IX (hFIX). Half of the animals administered with rAAV5-hSEAP underwent IA prior to the second rAAV5 exposure. The transduction efficacies of rAAV5-hSEAP and rAAV5-hFIX were assessed by measuring the levels of hSEAP and hFIX proteins. Although no hFIX was detected after rAAV5-hFIX readministration without prior IA, all animals submitted to IA showed therapeutic levels of hFIX expression, and a threshold of anti-AAV5 NAB levels compatible with successful readministration was demonstrated. In summary, our data demonstrate that the use of a clinically applicable IA procedure enables successful readministration of an rAAV5-based gene transfer in a clinically relevant animal model. Finally, the analysis of anti-AAV NAB levels in human subjects submitted to IA confirmed the safety and efficacy of the procedure to reduce anti-AAV NABs. Furthermore, clinical translation was assessed using an immunoglobulin G assay as surrogate.
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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.