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...

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Asıl Yazarlar: 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
Materyal Türü: Journal article
Dil:English
Baskı/Yayın Bilgisi: 2012
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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.
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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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