ArticleMolecular therapy : the journal of the American Society of Gene Therapy2017
5 Year Expression and Neutrophil Defect Repair after Gene Therapy in Alpha-1 Antitrypsin Deficiency.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers.
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Who cites it
69 citing papers in PubMed.
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- The co-delivery of Programmed Death 1 ligands enhances and prolongs rAAV-mediated gene expression in pre-immunized mice.Gene therapy · 2026Article
- Assessment of Immune Responses Against AAV Encoded Transgene Products.The AAPS journal · 2026Review
- Development of an AAV-delivered microRNA gene therapy for myotonic dystrophy type 1.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- AAV yield, bioactivity, and particle heterogeneity are impacted by genome size and non-coding DNA elements.Molecular therapy. Methods & clinical development · 2025Article
- The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Immune-driven gene expression loss following intramuscular AAV delivery to non-human primates is only transient.Molecular therapy. Methods & clinical development · 2025Article
- A comprehensive analysis of scRNA-Seq and RNA-Seq unveils B cell immune suppression in the AAV-loaded brain.Immunologic research · 2025Article
- A peptide conjugate enables systemic injection of the morpholino inducer and more durable induction of T3H38 ribozyme-controlled AAV transgene in mice.Gene therapy · 2025Article
- Reversion of metabolic dysfunction-associated steatohepatitis by skeletal muscle-directed FGF21 gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Adeno-Associated Virus Gene Transfer Ameliorates Progression of Skeletal Lesions in Mucopolysaccharidosis IVA Mice.Human gene therapy · 2024Article
- Global seroprevalence of neutralizing antibodies against adeno-associated virus serotypes used for human gene therapies.Molecular therapy. Methods & clinical development · 2024Article
- Article
- Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.Biomedicines · 2024Review
- Role of FoxP3Human gene therapy · 2024Review
- Biodistribution and safety of a single rAAV3B-AAT vector for silencing and replacement of alpha-1 antitrypsin inMolecular therapy. Methods & clinical development · 2024Article
- Identification of host essential factors for recombinant AAV transduction of the polarized human airway epithelium.Journal of virology · 2023Article
- Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells.International journal of molecular sciences · 2023Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors.
Funding
Abstract
Alpha-1 antitrypsin deficiency is a monogenic disorder resulting in emphysema due principally to the unopposed effects of neutrophil elastase. We previously reported achieving plasma wild-type alpha-1 antitrypsin concentrations at 2.5%-3.8% of the purported therapeutic level at 1 year after a single intramuscular administration of recombinant adeno-associated virus serotype 1 alpha-1 antitrypsin vector in alpha-1 antitrypsin deficient patients. We analyzed blood and muscle for alpha-1 antitrypsin expression and immune cell response. We also assayed previously reported markers of neutrophil function known to be altered in alpha-1 antitrypsin deficient patients. Here, we report sustained expression at 2.0%-2.5% of the target level from years 1-5 in these same patients without any additional recombinant adeno-associated virus serotype-1 alpha-1 antitrypsin vector administration. In addition, we observed partial correction of disease-associated neutrophil defects, including neutrophil elastase inhibition, markers of degranulation, and membrane-bound anti-neutrophil antibodies. There was also evidence of an active T regulatory cell response (similar to the 1 year data) and an exhausted cytotoxic T cell response to adeno-associated virus serotype-1 capsid. These findings suggest that muscle-based alpha-1 antitrypsin gene replacement is tolerogenic and that stable levels of M-AAT may exert beneficial neutrophil effects at lower concentrations than previously anticipated.
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