ArticleProceedings of the National Academy of Sciences of the United States of America1998
Sustained secretion of human alpha-1-antitrypsin from murine muscle transduced with adeno-associated virus vectors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 112 papers.
What it found
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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.
Preclinical & Phase I/II Trials of AAV-AAT Vectors: Phase I Trial of Intramuscular Injection of a Recombinant Adeno-Associated Virus Alpha 1-Antitrypsin (rAAV2-CB-hAAT) Gene Vector to AAT-Deficient Adults
Preclinical & Phase I/II Trials of AAV-AAT Vectors: Phase I Trial of Intramuscular Injection of a Recombinant Adeno-Associated Virus Alpha 1-Antitrypsin (rAAV1-CB-hAAT) Gene Vector to AAT-Deficient Adults
Who cites it
112 citing papers in PubMed.
- Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing α1-antitrypsin: interim results.Human gene therapy · 2011Trial
- Trial
- A compact base editor rescues AATD-associated liver and lung disease in mouse models.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- Secretion of functional α1-antitrypsin is cell type dependent: Implications for intramuscular delivery for gene therapy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Liver-directedMolecular therapy. Methods & clinical development · 2022Article
- Evaluation of cytosine base editing and adenine base editing as a potential treatment for alpha-1 antitrypsin deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Article
- Novel Combinatorial MicroRNA-Binding Sites in AAV Vectors Synergistically Diminish Antigen Presentation and Transgene Immunity for Efficient and Stable Transduction.Frontiers in immunology · 2021Article
- Gene Therapy in Rare Respiratory Diseases: What Have We Learned So Far?Journal of clinical medicine · 2020Review
- Gene therapy for alpha 1-antitrypsin deficiency with an oxidant-resistant human alpha 1-antitrypsin.JCI insight · 2020Article
- AAV-mediated expression of 3TSR inhibits tumor and metastatic lesion development and extends survival in a murine model of epithelial ovarian carcinoma.Cancer gene therapy · 2020Article
- Muscle-Directed Delivery of an AAV1 Vector Leads to Capsid-Specific T Cell Exhaustion in Nonhuman Primates and Humans.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Immune-orthogonal orthologues of AAV capsids and of Cas9 circumvent the immune response to the administration of gene therapy.Nature biomedical engineering · 2019Article
- Recombinant Adeno-Associated Virus Gene Therapy in Light of Luxturna (and Zolgensma and Glybera): Where Are We, and How Did We Get Here?Annual review of virology · 2019Article
- Regulated hAAT Expression from a Novel rAAV Vector and Its Application in the Prevention of Type 1 Diabetes.Journal of clinical medicine · 2019Article
- Alpha-1 Antitrypsin Therapy for Autoimmune Disorders.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2018Article
- Intrapleural Gene Therapy for Alpha-1 Antitrypsin Deficiency-Related Lung Disease.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2018Article
- In Vivo Genome Editing Partially Restores Alpha1-Antitrypsin in a Murine Model of AAT Deficiency.Human gene therapy · 2018Article
- Nuclease-Mediated Gene Therapies for Inherited Metabolic Diseases of the Liver.The Yale journal of biology and medicine · 2017Review
- 5 Year Expression and Neutrophil Defect Repair after Gene Therapy in Alpha-1 Antitrypsin Deficiency.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
52 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Recombinant adeno-associated virus (AAV) vectors have been used to transduce murine skeletal muscle as a platform for secretion of therapeutic proteins. The utility of this approach for treating alpha-1-antitrypsin (AAT) deficiency was tested in murine myocytes in vitro and in vivo. AAV vectors expressing the human AAT gene from either the cytomegalovirus (CMV) promoter (AAV-C-AT) or the human elongation factor 1-alpha promoter (AAV-E-AT) were examined. In vitro in C2C12 murine myoblasts, the expression levels in transient transfections were similar between the two vectors. One month after transduction, however, the human elongation factor 1 promoter mediated 10-fold higher stable human AAT expression than the CMV promoter. In vivo transduction was performed by injecting doses of up to 1.4 x 10(13) particles into skeletal muscles of several mouse strains (C57BL/6, BALB/c, and SCID). In vivo, the CMV vector mediated higher levels of expression, with sustained serum levels over 800 micrograms/ml in SCID and over 400 micrograms/ml in C57BL/6 mice. These serum concentrations are 100,000-fold higher than those previously observed with AAV vectors in muscle and are at levels which would be therapeutic if achieved in humans. High level expression was delayed for several weeks but was sustained for over 15 wk. Immune responses were dependent upon the mouse strain and the vector dosage. These data suggest that recombinant AAV vector transduction of skeletal muscle could provide a means for replacing AAT or other essential serum proteins but that immune responses may be elicited under certain conditions.
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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.