Trial reportThe Journal of clinical investigation2013
Human Treg responses allow sustained recombinant adeno-associated virus-mediated transgene expression.
Trial report in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01054339 (A Multiple-Site, Phase 2, Safety and Efficacy Trial of a Recombinant Adeno-associated Virus Vector Expressing Alpha-1 Antitrypsin), which is not on this map. Cited by 100 papers, 1 of them a synthesis that pooled it.
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.
A Multiple-Site, Phase 2, Safety and Efficacy Trial of a Recombinant Adeno-associated Virus Vector Expressing Alpha-1 Antitrypsin (rAAV1-CB-hAAT) in Patients With Alpha-1 Antitrypsin Deficiency
Who cites it
100 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.
- A systematic review of immunosuppressive protocols used in AAV gene therapy for monogenic disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Pooled it
- Class I-restricted T-cell responses to a polymorphic peptide in a gene therapy clinical trial for α-1-antitrypsin deficiency.Proceedings of the National Academy of Sciences of the United States of America · 2017Trial
- Immune responses to intramuscular administration of alipogene tiparvovec (AAV1-LPL(S447X)) in a phase II clinical trial of lipoprotein lipase deficiency gene therapy.Human gene therapy · 2014Trial
- CD8+ T cell activation occurs 24 hours after AAV administration and is driven by muscle promoter specificity.JCI insight · 2026Article
- Taming immune responses to AAV gene therapy by programmed in vivo Treg expansion.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Strategies for Evading Cellular Immunity Against Recombinant AAV Vectors in Gene Therapy.Current medical science · 2026Review
- The co-delivery of Programmed Death 1 ligands enhances and prolongs rAAV-mediated gene expression in pre-immunized mice.Gene therapy · 2026Article
- Expanding the Potential of Gene Therapy for Duchenne Muscular Dystrophy.Current pharmaceutical design · 2026Review
- SERPINA1 gene regulates the tumorigenesis and progression of breast cancer through PI3K/AKT signaling pathway and tumor immune microenvironment.Scientific reports · 2025Article
- The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Incomplete elimination of viral genomes is associated with chronic inflammation in nonhuman primate livers after AAV-mediated gene transfer.Gene therapy · 2025Article
- Immune-driven gene expression loss following intramuscular AAV delivery to non-human primates is only transient.Molecular therapy. Methods & clinical development · 2025Article
- Article
- Role of FoxP3Human gene therapy · 2024Review
- SERCA2a overexpression improves muscle function in a canine Duchenne muscular dystrophy model.Molecular therapy. Methods & clinical development · 2024Article
- Biodistribution and safety of a single rAAV3B-AAT vector for silencing and replacement of alpha-1 antitrypsin inMolecular therapy. Methods & clinical development · 2024Article
- Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells.International journal of molecular sciences · 2023Article
- Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Immune Responses to Muscle-Directed Adeno-Associated Viral Gene Transfer in Clinical Studies.Human gene therapy · 2023Review
- Evaluation of Cellular Immune Response to Adeno-Associated Virus-Based Gene Therapy.The AAPS journal · 2023Review
40 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
24 authors at 8 institutions in 3 countries.
Funding
Abstract
Recombinant adeno-associated virus (rAAV) vectors have shown promise for the treatment of several diseases; however, immune-mediated elimination of transduced cells has been suggested to limit and account for a loss of efficacy. To determine whether rAAV vector expression can persist long term, we administered rAAV vectors expressing normal, M-type α-1 antitrypsin (M-AAT) to AAT-deficient subjects at various doses by multiple i.m. injections. M-specific AAT expression was observed in all subjects in a dose-dependent manner and was sustained for more than 1 year in the absence of immune suppression. Muscle biopsies at 1 year had sustained AAT expression and a reduction of inflammatory cells compared with 3 month biopsies. Deep sequencing of the TCR Vβ region from muscle biopsies demonstrated a limited number of T cell clones that emerged at 3 months after vector administration and persisted for 1 year. In situ immunophenotyping revealed a substantial Treg population in muscle biopsy samples containing AAT-expressing myofibers. Approximately 10% of all T cells in muscle were natural Tregs, which were activated in response to AAV capsid. These results suggest that i.m. delivery of rAAV type 1-AAT (rAAV1-AAT) induces a T regulatory response that allows ongoing transgene expression and indicates that immunomodulatory treatments may not be necessary for rAAV-mediated gene therapy.
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.