title: Perfluorochemical liquid enhances adeno-associated virus-mediated transgene expression in lungs.
abstract: Use of adeno-associated virus (AAV) vectors for lung gene therapy is limited, in part, by low levels of AAV-mediated transgene expression in lungs. Generally, less than 1% of total airway and alveolar epithelial cells express transgene activity following vector administration. A means of improving AAV vector delivery could potentially enhance AAV-mediated gene expression in lungs. We have previously demonstrated that use of perfluorochemical (PFC) liquids improved overall levels of adenovirus vector-mediated gene expression as well as distribution of expression in lungs of spontaneously breathing rodents. To evaluate whether use of PFC liquids might similarly enhance AAV-mediated expression, spontaneously breathing rodents received intratracheal instillation of the AAV vectors CWRAP and ARAP4 (2-5 x 10(8) FFU/animal) with or without 10 cc/kg body wt PFC liquid (FC-75, ACROS). Animals were sacrificed 4 weeks later and lungs assessed for overall and in situ alkaline phosphatase (AP) expression. Animals receiving vector alone exhibited scattered sparse in situ activity, predominantly in alveolar epithelium. In contrast, animals receiving vector with FC-75 exhibited increased and more widespread AP expression as well as up to a 26-fold increase in AP activity. These results demonstrate that use of the PFC liquid FC-75 improves overall and in situ AAV-mediated gene expression in rodent lungs.
authors: Division of Pulmonary and Critical Care Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. dweiss@fhcrc.org
authors: D J
authors: DJ
authors: Weiss
authors: L
authors: L
authors: Bonneau
authors: J M
authors: JM
authors: Allen
authors: A D
authors: AD
authors: Miller
authors: C L
authors: CL
authors: Halbert
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D005466:Fluorocarbons / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D005822:Genetic Vectors; D006801:Humans; D008168:Lung / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051381:Rats; D017207:Rats, Sprague-Dawley; D019076:Transgenes; D014407:Tumor Cells, Cultured
chemical_list: D005466:Fluorocarbons