Correction of a chronic pulmonary disease through lentiviral vector-mediated protein expression
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 prot...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Molecular Therapy: Methods & Clinical Development |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2329050122000493 |
| _version_ | 1811309047359471616 |
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| author | Helena Lund-Palau Claudia Ivette Juarez-Molina Cuixiang Meng Anushka Bhargava Aikaterini Pilou Kiran Aziz Nora Clarke Naoko Atsumi Ali Ashek Michael R. Wilson Masao Takata Simon Padley Deborah R. Gill Stephen C. Hyde Cliff Morgan Eric W.F.W. Alton Uta Griesenbach |
| author_facet | Helena Lund-Palau Claudia Ivette Juarez-Molina Cuixiang Meng Anushka Bhargava Aikaterini Pilou Kiran Aziz Nora Clarke Naoko Atsumi Ali Ashek Michael R. Wilson Masao Takata Simon Padley Deborah R. Gill Stephen C. Hyde Cliff Morgan Eric W.F.W. Alton Uta Griesenbach |
| author_sort | Helena Lund-Palau |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T09:34:18Z |
| format | Article |
| id | doaj.art-4c2433997a7f402b8741006400d6273c |
| institution | Directory Open Access Journal |
| issn | 2329-0501 |
| language | English |
| last_indexed | 2024-04-13T09:34:18Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj.art-4c2433997a7f402b8741006400d6273c2022-12-22T02:52:08ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012022-06-0125382391Correction of a chronic pulmonary disease through lentiviral vector-mediated protein expressionHelena Lund-Palau0Claudia Ivette Juarez-Molina1Cuixiang Meng2Anushka Bhargava3Aikaterini Pilou4Kiran Aziz5Nora Clarke6Naoko Atsumi7Ali Ashek8Michael R. Wilson9Masao Takata10Simon Padley11Deborah R. Gill12Stephen C. Hyde13Cliff Morgan14Eric W.F.W. Alton15Uta Griesenbach16National Heart and Lung Institute, Gene Therapy Group, Imperial College London, Faculty of Medicine, Manresa Road, London SW3 6LR, UK; UK Respiratory Gene Therapy Consortium, London SW3 6LR, UKNational Heart and Lung Institute, Gene Therapy Group, Imperial College London, Faculty of Medicine, Manresa Road, London SW3 6LR, UK; UK Respiratory Gene Therapy Consortium, London SW3 6LR, UKNational Heart and Lung Institute, Gene Therapy Group, Imperial College London, Faculty of Medicine, Manresa Road, London SW3 6LR, UKNational Heart and Lung Institute, Gene Therapy Group, Imperial College London, Faculty of Medicine, Manresa Road, London SW3 6LR, UK; UK Respiratory Gene Therapy Consortium, London SW3 6LR, UKNational Heart and Lung Institute, Gene Therapy Group, Imperial College London, Faculty of Medicine, Manresa Road, London SW3 6LR, UK; UK Respiratory Gene Therapy Consortium, London SW3 6LR, UKNational Heart and Lung Institute, Gene Therapy Group, Imperial College London, Faculty of Medicine, Manresa Road, London SW3 6LR, UK; UK Respiratory Gene Therapy Consortium, London SW3 6LR, UKNational Heart and Lung Institute, Gene Therapy Group, Imperial College London, Faculty of Medicine, Manresa Road, London SW3 6LR, UK; UK Respiratory Gene Therapy Consortium, London SW3 6LR, UKNational Heart and Lung Institute, Gene Therapy Group, Imperial College London, Faculty of Medicine, Manresa Road, London SW3 6LR, UK; UK Respiratory Gene Therapy Consortium, London SW3 6LR, UKNational Heart and Lung Institute, Gene Therapy Group, Imperial College London, Faculty of Medicine, Manresa Road, London SW3 6LR, UKDivision of Anesthetics, Pain Medicine, and Intensive Care, Department of Surgery and Cancer, Imperial College London, London, UKDivision of Anesthetics, Pain Medicine, and Intensive Care, Department of Surgery and Cancer, Imperial College London, London, UKRoyal Brompton Hospital & Harefield Hospitals, London, UKRadcliffe Department of Medicine, University of Oxford, Oxford, UK; UK Respiratory Gene Therapy Consortium, London SW3 6LR, UKRadcliffe Department of Medicine, University of Oxford, Oxford, UK; UK Respiratory Gene Therapy Consortium, London SW3 6LR, UKRoyal Brompton Hospital & Harefield Hospitals, London, UKNational Heart and Lung Institute, Gene Therapy Group, Imperial College London, Faculty of Medicine, Manresa Road, London SW3 6LR, UK; UK Respiratory Gene Therapy Consortium, London SW3 6LR, UK; Corresponding author Eric W.F.W. Alton, National Heart and Lung Institute, Gene Therapy Group, Imperial College London, Faculty of Medicine, Manresa Road, London SW3 6LR, UK.National Heart and Lung Institute, Gene Therapy Group, Imperial College London, Faculty of Medicine, Manresa Road, London SW3 6LR, UK; UK Respiratory Gene Therapy Consortium, London SW3 6LR, UKWe 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.http://www.sciencedirect.com/science/article/pii/S2329050122000493autoimmune pulmonary alveolar proteinosisPAPalveolar macrophagesurfactant proteingranulocyte-macrophage colony-stimulating factorGM-CSF |
| spellingShingle | Helena Lund-Palau Claudia Ivette Juarez-Molina Cuixiang Meng Anushka Bhargava Aikaterini Pilou Kiran Aziz Nora Clarke Naoko Atsumi Ali Ashek Michael R. Wilson Masao Takata Simon Padley Deborah R. Gill Stephen C. Hyde Cliff Morgan Eric W.F.W. Alton Uta Griesenbach Correction of a chronic pulmonary disease through lentiviral vector-mediated protein expression Molecular Therapy: Methods & Clinical Development autoimmune pulmonary alveolar proteinosis PAP alveolar macrophage surfactant protein granulocyte-macrophage colony-stimulating factor GM-CSF |
| title | Correction of a chronic pulmonary disease through lentiviral vector-mediated protein expression |
| title_full | Correction of a chronic pulmonary disease through lentiviral vector-mediated protein expression |
| title_fullStr | Correction of a chronic pulmonary disease through lentiviral vector-mediated protein expression |
| title_full_unstemmed | Correction of a chronic pulmonary disease through lentiviral vector-mediated protein expression |
| title_short | Correction of a chronic pulmonary disease through lentiviral vector-mediated protein expression |
| title_sort | correction of a chronic pulmonary disease through lentiviral vector mediated protein expression |
| topic | autoimmune pulmonary alveolar proteinosis PAP alveolar macrophage surfactant protein granulocyte-macrophage colony-stimulating factor GM-CSF |
| url | http://www.sciencedirect.com/science/article/pii/S2329050122000493 |
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