Assessment of F/HN-pseudotyped lentivirus as a clinically relevant vector for lung gene therapy.
RATIONALE: Ongoing efforts to improve pulmonary gene transfer thereby enabling gene therapy for the treatment of lung diseases, such as cystic fibrosis (CF), has led to the assessment of a lentiviral vector (simian immunodeficiency virus [SIV]) pseudotyped with the Sendai virus envelope proteins F a...
| Главные авторы: | , , , , , , , , , , , , , , , , , , |
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| Формат: | Journal article |
| Язык: | English |
| Опубликовано: |
2012
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| _version_ | 1826257985032159232 |
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| author | Griesenbach, U Inoue, M Meng, C Farley, R Chan, M Newman, N Brum, A You, J Kerton, A Shoemark, A Boyd, A Davies, J Higgins, T Gill, DR Hyde, S Innes, J Porteous, D Hasegawa, M Alton, E |
| author_facet | Griesenbach, U Inoue, M Meng, C Farley, R Chan, M Newman, N Brum, A You, J Kerton, A Shoemark, A Boyd, A Davies, J Higgins, T Gill, DR Hyde, S Innes, J Porteous, D Hasegawa, M Alton, E |
| author_sort | Griesenbach, U |
| collection | OXFORD |
| description | RATIONALE: Ongoing efforts to improve pulmonary gene transfer thereby enabling gene therapy for the treatment of lung diseases, such as cystic fibrosis (CF), has led to the assessment of a lentiviral vector (simian immunodeficiency virus [SIV]) pseudotyped with the Sendai virus envelope proteins F and HN. OBJECTIVES: To place this vector onto a translational pathway to the clinic by addressing some key milestones that have to be achieved. METHODS: F/HN-SIV transduction efficiency, duration of expression, and toxicity were assessed in mice. In addition, F/HN-SIV was assessed in differentiated human air-liquid interface cultures, primary human nasal epithelial cells, and human and sheep lung slices. MEASUREMENTS AND MAIN RESULTS: A single dose produces lung expression for the lifetime of the mouse (~2 yr). Only brief contact time is needed to achieve transduction. Repeated daily administration leads to a dose-related increase in gene expression. Repeated monthly administration to mouse lower airways is feasible without loss of gene expression. There is no evidence of chronic toxicity during a 2-year study period. F/HN-SIV leads to persistent gene expression in human differentiated airway cultures and human lung slices and transduces freshly obtained primary human airway epithelial cells. CONCLUSIONS: The data support F/HN-pseudotyped SIV as a promising vector for pulmonary gene therapy for several diseases including CF. We are now undertaking the necessary refinements to progress this vector into clinical trials. |
| first_indexed | 2024-03-06T18:26:51Z |
| format | Journal article |
| id | oxford-uuid:0844e52f-bf7b-4e7d-a7c6-239eb7d604bf |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:26:51Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:0844e52f-bf7b-4e7d-a7c6-239eb7d604bf2022-03-26T09:11:58ZAssessment of F/HN-pseudotyped lentivirus as a clinically relevant vector for lung gene therapy.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:0844e52f-bf7b-4e7d-a7c6-239eb7d604bfEnglishSymplectic Elements at Oxford2012Griesenbach, UInoue, MMeng, CFarley, RChan, MNewman, NBrum, AYou, JKerton, AShoemark, ABoyd, ADavies, JHiggins, TGill, DRHyde, SInnes, JPorteous, DHasegawa, MAlton, ERATIONALE: Ongoing efforts to improve pulmonary gene transfer thereby enabling gene therapy for the treatment of lung diseases, such as cystic fibrosis (CF), has led to the assessment of a lentiviral vector (simian immunodeficiency virus [SIV]) pseudotyped with the Sendai virus envelope proteins F and HN. OBJECTIVES: To place this vector onto a translational pathway to the clinic by addressing some key milestones that have to be achieved. METHODS: F/HN-SIV transduction efficiency, duration of expression, and toxicity were assessed in mice. In addition, F/HN-SIV was assessed in differentiated human air-liquid interface cultures, primary human nasal epithelial cells, and human and sheep lung slices. MEASUREMENTS AND MAIN RESULTS: A single dose produces lung expression for the lifetime of the mouse (~2 yr). Only brief contact time is needed to achieve transduction. Repeated daily administration leads to a dose-related increase in gene expression. Repeated monthly administration to mouse lower airways is feasible without loss of gene expression. There is no evidence of chronic toxicity during a 2-year study period. F/HN-SIV leads to persistent gene expression in human differentiated airway cultures and human lung slices and transduces freshly obtained primary human airway epithelial cells. CONCLUSIONS: The data support F/HN-pseudotyped SIV as a promising vector for pulmonary gene therapy for several diseases including CF. We are now undertaking the necessary refinements to progress this vector into clinical trials. |
| spellingShingle | Griesenbach, U Inoue, M Meng, C Farley, R Chan, M Newman, N Brum, A You, J Kerton, A Shoemark, A Boyd, A Davies, J Higgins, T Gill, DR Hyde, S Innes, J Porteous, D Hasegawa, M Alton, E Assessment of F/HN-pseudotyped lentivirus as a clinically relevant vector for lung gene therapy. |
| title | Assessment of F/HN-pseudotyped lentivirus as a clinically relevant vector for lung gene therapy. |
| title_full | Assessment of F/HN-pseudotyped lentivirus as a clinically relevant vector for lung gene therapy. |
| title_fullStr | Assessment of F/HN-pseudotyped lentivirus as a clinically relevant vector for lung gene therapy. |
| title_full_unstemmed | Assessment of F/HN-pseudotyped lentivirus as a clinically relevant vector for lung gene therapy. |
| title_short | Assessment of F/HN-pseudotyped lentivirus as a clinically relevant vector for lung gene therapy. |
| title_sort | assessment of f hn pseudotyped lentivirus as a clinically relevant vector for lung gene therapy |
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