ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Neonatal Systemic AAV Induces Tolerance to CNS Gene Therapy in MPS I Dogs and Nonhuman Primates.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.
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Who cites it
65 citing papers in PubMed, 83 citations in OpenAlex.
- Adeno-associated virus delivery of anti-alpha toxin monoclonal antibodies confers protection against Staphylococcus aureus infections.PLoS pathogens · 2026Article
- AAV-mediated gene therapy for the CNS: The case for early treatment.Molecular therapy. Methods & clinical development · 2025Article
- Is dystrophin immunogenicity a barrier to advancing gene therapy for Duchenne muscular dystrophy?Gene therapy · 2025Review
- Early postnatal expression mitigates immune responses to Cas9 in the murine central nervous system.Molecular therapy. Methods & clinical development · 2025Article
- Teaching an old vector new tricks: the surprising versatility of AAV vaccines.Journal of virology · 2025Review
- In vivo evolution of env in SHIV-AD8Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Intrathecal or intravenous AAV9-IDUA/RGX-111 at minimal effective dose prevents cardiac, skeletal and neurologic manifestations of murine MPS I.Molecular therapy. Methods & clinical development · 2024Article
- Liver-directed AAV gene therapy normalizes disease symptoms and provides cross-correction in a model of lysosomal acid lipase deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Gene therapy of Dent disease type 1 in newborn ClC-5 null mice for sustained transgene expression and gene therapy effects.Gene therapy · 2024Article
- Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.Biomedicines · 2024Review
- AAV-vectored expression of monospecific or bispecific monoclonal antibodies protects mice from lethal Pseudomonas aeruginosa pneumonia.Gene therapy · 2024Article
- Recent Advances in In Vivo Somatic Cell Gene Modification in Newborn Pups.International journal of molecular sciences · 2023Review
- Targeting the central nervous system in lysosomal storage diseases: Strategies to deliver therapeutics across the blood-brain barrier.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- In vivo adenine base editing corrects newborn murine model of Hurler syndrome.Molecular biomedicine · 2023Article
- Intra-Articular AAV9Advances in cell and gene therapy · 2023Article
- Neurologic Recovery in MPS I and MPS II Mice by AAV9-Mediated Gene Transfer to the CNS After the Development of Cognitive Dysfunction.Human gene therapy · 2023Article
- Dystrophin immunogenicity and requirement in myogenic cells: Paradigm shift in gene therapy for DMD.Clinical and translational medicine · 2022Article
- MPSI Manifestations and Treatment Outcome: Skeletal Focus.International journal of molecular sciences · 2022Review
- Efficacy and Safety of a Krabbe Disease Gene Therapy.Human gene therapy · 2022Article
- Delivering gene therapy for mucopolysaccharide diseases.Frontiers in molecular biosciences · 2022Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 2 institutions in 1 country.
Funding
Abstract
The potential host immune response to a nonself protein poses a fundamental challenge for gene therapies targeting recessive diseases. We demonstrate in both dogs and nonhuman primates that liver-directed gene transfer using an adeno-associated virus (AAV) vector in neonates induces a persistent state of immunological tolerance to the transgene product, substantially improving the efficacy of subsequent vector administration targeting the central nervous system (CNS). We applied this approach to a canine model of mucopolysaccharidosis type I (MPS I), a progressive neuropathic lysosomal storage disease caused by deficient activity of the enzyme α-l-iduronidase (IDUA). MPS I dogs treated systemically in the first week of life with a vector expressing canine IDUA did not develop antibodies against the enzyme and exhibited robust expression in the CNS upon intrathecal AAV delivery at 1 month of age, resulting in complete correction of brain storage lesions. Newborn rhesus monkeys treated systemically with AAV vector expressing human IDUA developed tolerance to the transgene, resulting in high cerebrospinal fluid (CSF) IDUA expression and no antibody induction after subsequent CNS gene therapy. These findings suggest that inducing tolerance to the transgene product during a critical period in immunological development can improve the efficacy and safety of gene therapy.
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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.