Lentiviral airway gene transfer in lungs of mice and sheep: successes and challenges

The Journal of Gene Medicine
Chuanhe LiuDavid W Parsons

Abstract

Persistent airway gene expression can be achieved in mouse nasal airway using a vesicular stomatitis virus glycoprotein pseudotyped lentiviral (LV) gene vector in combination with lysophosphatidylcholine (LPC) pretreatment. We have now examined the acute in vivo effects of this combination single-dose method for airway LV gene transfer in mouse and sheep lung. Mouse and sheep lungs were exposed to LPC followed 1 h later with the LV vector. Lungs were processed 7 days later using X-gal detection to measure beta-gal gene expression and identify transduced cell types. In mouse ciliated conducting airways, LPC pretreatment produced extensive gene transfer that extended from the tracheal dosing site into the bronchi and lower airways. Gene expression was present in both terminally differentiated surface cells and in basal cells. Without LPC pretreatment, transduction was limited to the dosing site. In sheep lung, small-volume bronchoscopic instillation delivery produced localized and low-level transduction near the dosing site. Gene expression was again present in surface and basal cells. Neither alterations in LPC dose parameters, nor larger vector volumes increased the level of transduction. These findings are the first to confirm...Continue Reading

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Citations

Jun 19, 2018·Veterinary Sciences·Garyfalia KarponiEleni Papanikolaou
Jul 16, 2013·Current Protocols in Human Genetics·Nicholas W Keiser, John F Engelhardt
Dec 13, 2018·Frontiers in Pharmacology·Martin Donnelley, David W Parsons

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