ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Expression of human alpha1-antitrypsin in mice and dogs following AAV6 vector-mediated gene transfer to the lungs.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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.
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Who cites it
28 citing papers in PubMed, 39 citations in OpenAlex.
- Phase 2 clinical trial of a recombinant adeno-associated viral vector expressing α1-antitrypsin: interim results.Human gene therapy · 2011Trial
- A highly mobile adeno-associated virus targeting vascular smooth muscle cells for the treatment of pulmonary arterial hypertension.Nature biomedical engineering · 2025Article
- Review
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- Structural basis for nuclear import of adeno-associated virus serotype 6 capsid protein.Journal of virology · 2025Article
- Review
- Liver-directedMolecular therapy. Methods & clinical development · 2022Article
- Intra-tracheal delivery of AAV6 vectors results in sustained transduction in murine lungs without genomic integration.Gene: X · 2020Article
- Gene therapy for alpha 1-antitrypsin deficiency with an oxidant-resistant human alpha 1-antitrypsin.JCI insight · 2020Article
- Intrapleural Gene Therapy for Alpha-1 Antitrypsin Deficiency-Related Lung Disease.Chronic obstructive pulmonary diseases (Miami, Fla.) · 2018Article
- The murine lung as a factory to produce secreted intrapulmonary and circulatory proteins.Gene therapy · 2018Article
- Barriers to inhaled gene therapy of obstructive lung diseases: A review.Journal of controlled release : official journal of the Controlled Release Society · 2016Review
- Is It All in the Eye of the Beholder? Comparing Pulmonologists' and Radiologists' Performance.Federal practitioner : for the health care professionals of the VA, DoD, and PHS · 2016Article
- Gene Therapy for Alpha-1 Antitrypsin Deficiency Lung Disease.Annals of the American Thoracic Society · 2016Review
- Vector serotype screening for use in ovine perinatal lung gene therapy.Journal of pediatric surgery · 2016Article
- Recombinant Adeno-Associated Virus Vector Genomes Take the Form of Long-Lived, Transcriptionally Competent Episomes in Human Muscle.Human gene therapy · 2016Article
- Challenges and Prospects for Alpha-1 Antitrypsin Deficiency Gene Therapy.Human gene therapy · 2015Review
- Robust Lentiviral Gene Delivery But Limited Transduction Capacity of Commonly Used Adeno-Associated Viral Serotypes in Xenotransplanted Human Skin.Human gene therapy methods · 2015Article
- Cystic Fibrosis Gene Therapy in the UK and Elsewhere.Human gene therapy · 2015Review
- Translational data from adeno-associated virus-mediated gene therapy of hemophilia B in dogs.Human gene therapy. Clinical development · 2015Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
We evaluated the potential of lung-directed gene therapy for alpha1-antitrypsin (AAT) deficiency using an adeno-associated virus type 6 (AAV6) vector containing a human AAT (hAAT) complementary DNA (cDNA) delivered to the lungs of mice and dogs. The results in normal and immune-deficient mice showed that hAAT concentrations were much higher in lung fluid than in plasma, and therapeutic levels were obtained even in normal mice. However, in normal mice an immune response against the vector and/or transgene limited long-term gene expression. An AAV6 vector expressing a marker protein verified that AAV6 vectors efficiently transduced lung cells in dogs. Delivery of AAV6-hAAT resulted in low levels of hAAT in dog serum but therapeutic levels in the lung that persisted for at least 58 days to 4 months in three immunosuppressed dogs. Expression in the serum was not detectable after 45 days in one nonimmune suppressed dog. A lymphoproliferative response to AAV capsid but not to hAAT was detected even after immunosuppression. These results in mice and dogs show the feasibility of expression of therapeutic levels of AAT in the lungs after AAV vector delivery, and advocate for approaches to prevent cellular immune responses to AAV capsid proteins for persistence of gene expression in humans.
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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.