ArticleMolecular therapy : the journal of the American Society of Gene Therapy2022
Non-invasive administration of AAV to target lung parenchymal cells and develop SARS-CoV-2-susceptible mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
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- Distinct HIF1α and HIF2α functions control skeletal muscle metabolism and erythropoiesis.The Journal of clinical investigation · 2026Article
- Pulmonary Vascular Endothelial Cells in Lung Diseases: Mechanisms, Therapeutic Strategies, and Future Directions.Cell proliferation · 2026Review
- Thioredoxin-interacting protein as a crucial regulator in asthma exacerbation induced by copper oxide nanoparticles in a mouse model.Redox biology · 2025Article
- Review
- Copper oxide nanoparticles exacerbate chronic obstructive pulmonary disease by activating the TXNIP-NLRP3 signaling pathway.Particle and fibre toxicology · 2024Article
- CasRx-based Wnt activation promotes alveolar regeneration while ameliorating pulmonary fibrosis in a mouse model of lung injury.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- SARS-CoV-2-Specific T-Cell as a Potent Therapeutic Strategy against Immune Evasion of Emerging COVID-19 Variants.International journal of molecular sciences · 2024Article
- Emerging and reemerging infectious diseases: global trends and new strategies for their prevention and control.Signal transduction and targeted therapy · 2024Review
- AAV-based vectors for human diseases modeling in laboratory animals.Frontiers in medicine · 2024Review
- Efficient Adeno-associated Virus-mediated Transgenesis in Alveolar Stem Cells and Associated Niches.American journal of respiratory cell and molecular biology · 2023Article
- Article
- Population-wide gene disruption in the murine lung epithelium via AAV-mediated delivery of CRISPR-Cas9 components.Molecular therapy. Methods & clinical development · 2022Article
- Gene Therapeutics for Surfactant Dysfunction Disorders: Targeting the Alveolar Type 2 Epithelial Cell.Human gene therapy · 2022Review
- Animal models for COVID-19: advances, gaps and perspectives.Signal transduction and targeted therapy · 2022Review
- The Evolutionary Dance between Innate Host Antiviral Pathways and SARS-CoV-2.Pathogens (Basel, Switzerland) · 2022Review
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Authors and funding
16 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adeno-associated virus (AAV)-mediated gene delivery holds great promise for gene therapy. However, the non-invasive delivery of AAV for lung tissues has not been adequately established. Here, we revealed that the intratracheal administration of an appropriate amount of AAV2/8 predominantly targets lung tissue. AAV-mediated gene delivery that we used in this study induced the expression of the desired protein in lung parenchymal cells, including alveolar type II cells. We harnessed the technique to develop severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-susceptible mice. Three kinds of immune function-relevant gene knockout (KO) mice were transduced with AAV encoding human angiotensin-converting enzyme 2 (hACE2) and then injected with SARS-CoV-2. Among these mice, type I interferon receptor (IFNAR) KO mice showed increased viral titer in the lungs compared to that in the other KO mice. Moreover, nucleocapsid protein of SARS-CoV-2 and multiple lesions in the trachea and lung were observed in AAV-hACE2-transduced, SARS-CoV-2-infected IFNAR KO mice, indicating the involvement of type I interferon signaling in the protection of SARS-CoV-2. In this study, we demonstrate the ease and rapidness of the intratracheal administration of AAV for targeting lung tissue in mice, and this can be used to study diverse pulmonary diseases.
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