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Updated: Sep 23, 2025

Protein Transfection of Mouse Lung
Published on: May 15, 2013
Correction of a chronic pulmonary disease through lentiviral vector-mediated protein expression
Helena Lund-Palau1,2, Claudia Ivette Juarez-Molina1,2, Cuixiang Meng1
1National Heart and Lung Institute, Gene Therapy Group, Imperial College London, Faculty of Medicine, Manresa Road, London SW3 6LR, UK.
Abstract:
We developed a novel lentiviral vector, pseudotyped with the F and HN proteins from Sendai virus (rSIV.F/HN), that produces long-lasting, high-efficiency transduction of the respiratory epithelium. Here we addressed whether this platform technology can secrete sufficient levels of a therapeutic protein into the lungs to ameliorate a fatal pulmonary disease as an example of its translational capability. Pulmonary alveolar proteinosis (PAP) results from alveolar granulocyte-macrophage colony-stimulating factor (GM-CSF) insufficiency, resulting in abnormal surfactant homeostasis and consequent ventilatory problems. Lungs of GM-CSF knockout mice were transduced with a single dose of rSIV.F/HN-expressing murine GM-CSF (mGM-CSF; 1e5-92e7 transduction units [TU]/mouse); mGM-CSF expression was dose related and persisted for at least 11 months. PAP disease biomarkers were rapidly and persistently corrected, but we noted a narrow toxicity/efficacy window. rSIV.F/HN may be a useful platform technology to deliver therapeutic proteins for lung diseases requiring long-lasting and stable expression of secreted proteins.
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