BibTex format
@article{Paul-Smith:2018:10.1038/s41434-018-0025-8,
author = {Paul-Smith, M and Pytel, K and Gelinas, J-F and McIntosh, J and Pringle, I and Davies, L and Chan, M and Meng, C and Bell, R and Cammack, L and Moran, C and Cameron, L and Inoue, M and Tsugumine, S and Hironaka, T and Gill, D and Hyde, S and Nathwani, A and Alton, E and Griesenbach, U},
doi = {10.1038/s41434-018-0025-8},
journal = {Gene Therapy},
pages = {345--358},
title = {The murine lung as a factory to produce secreted intrapulmonary and circulatory proteins},
url = {http://dx.doi.org/10.1038/s41434-018-0025-8},
volume = {25},
year = {2018}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - We have shown that a lentiviral vector (rSIV.F/HN) pseudotyped with the F and HN proteins from Sendai virus generates high levels of intracellular proteins after lung transduction. Here, we evaluate the use of rSIV.F/HN for production of secreted proteins. We assessed whether rSIV.F/HN transduction of the lung generates therapeutically relevant levels of secreted proteins in the lung and systemic circulation using 1-anti-trypsin (hAAT) and factor VIII (hFVIII) as exemplars. Sedated mice were transduced with rSIV.F/HN carrying either the secreted reporter gene Gaussia luciferase (GLux) or the hAAT or hFVIII cDNAs by nasal sniffing.rSIV.F/HN-hAAT transduction lead to therapeutically relevant hAAT levels (70 g/ml) in ELF, with stable expression persisting for at least 19 months from a single application. Secreted proteins produced in the lung were released into the circulation and stable expression was detectable in blood. The levels of hFVIII in murine blood approached therapeutically relevant targets. rSIV.F/HN was also able to produce secreted hAAT and hFVIII in transduced human primary airway cells.rSIV.F/HN transduction of the murine lungs leads to long-lasting and therapeutically relevant levels of secreted proteins in the lung and systemic circulation. These data broaden the use of this vector platform for a large range of disease indications.
AU - Paul-Smith,M
AU - Pytel,K
AU - Gelinas,J-F
AU - McIntosh,J
AU - Pringle,I
AU - Davies,L
AU - Chan,M
AU - Meng,C
AU - Bell,R
AU - Cammack,L
AU - Moran,C
AU - Cameron,L
AU - Inoue,M
AU - Tsugumine,S
AU - Hironaka,T
AU - Gill,D
AU - Hyde,S
AU - Nathwani,A
AU - Alton,E
AU - Griesenbach,U
DO - 10.1038/s41434-018-0025-8
EP - 358
PY - 2018///
SN - 0969-7128
SP - 345
TI - The murine lung as a factory to produce secreted intrapulmonary and circulatory proteins
T2 - Gene Therapy
UR - http://dx.doi.org/10.1038/s41434-018-0025-8
UR - http://hdl.handle.net/10044/1/60209
VL - 25
ER -
