ArticleThe Journal of clinical investigation2010
Amelioration of emphysema in mice through lentiviral transduction of long-lived pulmonary alveolar macrophages.
Article in The Journal of clinical investigation, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 93 citations in OpenAlex.
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- Human pluripotent stem cell modeling of alveolar type 2 cell dysfunction caused by ABCA3 mutations.The Journal of clinical investigation · 2024Article
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- Loss of SP-A in the Lung Exacerbates Pulmonary Fibrosis.International journal of molecular sciences · 2022Article
- Gene therapy of Csf2ra deficiency in mouse fetal monocyte precursors restores alveolar macrophage development and function.JCI insight · 2022Article
- Gene Therapy: Will the Promise of Optimizing Lung Allografts Become Reality?Frontiers in immunology · 2022Review
- TREM-2 is a sensor and activator of T cell response in SARS-CoV-2 infection.Science advances · 2021Article
- A mouse model for the study of anti-tumor T cell responses in Kras-driven lung adenocarcinoma.Cell reports methods · 2021Article
- HIV-based lentiviral vectors: origin and sequence differences.Molecular therapy. Methods & clinical development · 2021Article
- Overexpression of alpha-1 antitrypsin in mesenchymal stromal cells improves their intrinsic biological properties and therapeutic effects in nonobese diabetic mice.Stem cells translational medicine · 2021Article
- Gene Therapy in Rare Respiratory Diseases: What Have We Learned So Far?Journal of clinical medicine · 2020Review
- Intratracheal aerosolization of viral vectors to newborn pig airways.BioTechniques · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Directed gene transfer into specific cell lineages in vivo is an attractive approach for both modulating gene expression and correcting inherited mutations such as emphysema caused by human alpha1 antitrypsin (hAAT) deficiency. However, somatic tissues are mainly comprised of heterogeneous, differentiated cell lineages that can be short lived and difficult to specifically transfect. Here, we describe an intratracheally instilled lentiviral system able to deliver genes selectively to as many as 70% of alveolar macrophages (AMs) in the mouse lung. Following a single in vivo lentiviral transduction, genetically tagged AMs persisted in lung alveoli and expressed transferred genes for the lifetime of the adult mouse. A prolonged macrophage lifespan, rather than precursor cell proliferation, accounted for the surprisingly sustained presence of transduced AMs. We utilized this long-lived population to achieve localized secretion of therapeutic levels of hAAT protein in lung epithelial lining fluid. In an established mouse model of emphysema, lentivirally delivered hAAT ameliorated the progression of emphysema, as evidenced by attenuation of increased lung compliance and alveolar size. After 24 weeks of sustained gene expression, no humoral or cellular immune responses to hAAT protein were detected. Our results challenge the dogma that AMs are short lived and suggest that these differentiated cells may be a possible target cell population for in vivo gene therapy applications, including the sustained correction of hAAT deficiency.
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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.