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 previous ly demonstrated that intratracheal instillation of perfluorochemical (PFC) liquids along with instillation of recombinant adenovirus and adeno-associa ted virus vectors,or with cationic liposome vectors, increased total lung g ene expression and enhanced distribution of gene expression throughout the lung. To further explore the potential benefits of PFC liquid use, we evalu ated the effect of PFC liquid instillation on several other aspects of aden ovirus-mediated gene expression in lung. Use of PFC liquid resulted in earl ier detection of gene expression and allowed the use of less vector to achi eve expression comparable to that observed with the use of higher amounts o f vector alone. Using PFC liquid also enhanced gene expression in a rodent model of acute lung injury. PFC liquid did cause a transient inflammation w hen instilled into normal lungs but did not cause any additional inflammati on when instilled alone or with adenovirus vector into acutely injured lung s. Thus, PFC liquid may be a useful adjunct for clinical lung gene transfer , particularly for injured or diseased lungs.