Use of perfluorochemical liquid allows earlier detection of gene expression and use of less vector in normal lung and enhances gene expression in acutely injured lung.
One of the obstacles to successful lung gene transfer is effective delivery of vector to lung, particularly injured or diseased lung. We have previously demonstrated that intratracheal instillation of perfluorochemical (PFC) liquids along with instillation of recombinant adenovirus and adeno-associated virus vectors, or with cationic liposome vectors, increased total lung gene expression and enhanced distribution of gene expression throughout the lung. To further explore the potential benefits of PFC liquid use, we evaluated the effect of PFC liquid instillation on several other aspects of adenovirus-mediated gene expression in lung. Use of PFC liquid resulted in earlier detection of gene expression and allowed the use of less vector to achieve expression comparable to that observed with the use of higher amounts of vector alone. Using PFC liquid also enhanced gene expression in a rodent model of acute lung injury. PFC liquid did cause a transient inflammation when instilled into normal lungs but did not cause any additional inflammation when instilled alone or with adenovirus vector into acutely injured lungs. Thus, PFC liquid may be a useful adjunct for clinical lung gene transfer, particularly for injured or diseased lungs.
Weiss
D J
DJ
Division of Pulmonary and Critical Care Medicine, Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue North, Seattle, WA 98109-1024, USA. dweiss@fhcrc.org
Bonneau
L
L
Liggitt
D
D
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D005465:Fluorocarbon Polymers / Q000737:chemistry*; D005466:Fluorocarbons / Q000737:chemistry; D005663:Furans / Q000737:chemistry; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism*; D055370:Lung Injury; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D019076:Transgenes; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D001616:beta-Galactosidase / Q000378:metabolism
D005465:Fluorocarbon Polymers; D005466:Fluorocarbons; D005663:Furans; D007375:Interleukin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C429307:fluorocarbon 77; C073032:perfluorobutyl tetrahydrofuran; D001616:beta-Galactosidase