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• W2775683477 abstract "Purpose/Aim: Cystic fibrosis (CF) is the most common, fatal recessive genetic disease among the Caucasian population. Gene therapy has the potential to treat CF long term, however physiological barriers can prevent VSV-G pseudotyped lentiviral (LV) vectors from efficiently accessing the relevant receptors on the basolateral membrane of airway epithelial cells. The aims of this experiment were to use our new dose delivery techniques to determine whether conditioning the mouse lung conducting airways with lysophosphatidylcholine (LPC) improves the level of airway gene expression. Materials and Methods: Anaesthetised normal C57Bl/6 mice were intubated with an endotracheal cannula to non-invasively facilitate airway access. The airways were conditioned with 0.1% LPC, 0.3% LPC, or PBS (control) instilled via the ET tube. One hour later a VSV-G pseudotyped LV vector carrying the LacZ transgene was delivered. LacZ expression was measured by X-gal staining of the excised lungs 3 months after gene delivery. Results: Endotracheal intubation enabled precise dose delivery to the trachea and conducting airways. The cartilaginous airways of the groups conditioned with 0.1% and 0.3% LPC contained significantly larger numbers of LacZ positive cells compared to the PBS control group. In the LPC conditioned groups the majority of cell transduction was in ciliated epithelial cells. Conclusion: LPC conditioning prior to LV vector delivery, substantially enhanced the level of conducting airway gene expression after a single gene vector delivery. These results extend the previously established effectiveness of this protocol for producing gene expression in the nasal airways to the lung airways, the primary site of deleterious pathophysiology in CF individuals." @default.
• W2775683477 created "2017-12-22" @default.
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• W2775683477 date "2017-11-26" @default.
• W2775683477 modified "2023-10-16" @default.
• W2775683477 title "Gene therapy for Cystic Fibrosis: Improved delivery techniques and conditioning with lysophosphatidylcholine enhance lentiviral gene transfer in mouse lung airways" @default.
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• W2775683477 doi "https://doi.org/10.1080/01902148.2017.1395931" @default.
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