Perfluorochemical Liquid-Adenovirus Suspensions Enhance Gene Delivery to the Distal Lung
PP2/PP9 suspensions improve transgene expression in the distal lung. Left Panel: whole mounts of lungs from mice transduced with rAd-CMVLacZ ( viral particles) administered intratracheally in (a) saline alone, (b) saline followed by a chase of PP2:PP9 (10 mL/kg), or (c) rAd/PP2:PP9 suspension. (a) Proximal airway expression is seen predominantly when rAd is delivered in saline alone. (b) Increased expression in proximal and distal lung is seen when delivery of the virus in saline is followed by a PP2:PP9 chase; (c) Greatest staining compared to the other methodologies in the alveolar spaces and the distal lung with delivery of rAd in PP2:PP9 suspensions. Middle Panel: lungs were removed, embedded in paraffin, and sectioned to the same approximate depth. Inset in middle panel C demonstrates a distinctly alveolar pattern in the PFC liquid/rAd lungs and a lack of staining in the corresponding region of the virus in saline is followed by a PP2:PP9 chase (inset, middle panel (b)). Right Panel: sections were mounted on slides and counterstained with eosin.. When rAd is delivered in saline (right panel (a)), the signal was predominantly detected in the central airways with very little β-gal expression seen in the lung parenchyma. With virus delivered in saline followed by a PP2:PP9 chase (right panel (b)), there is an increase in the intensity of staining in the corresponding regions of the airways with more evidence of peripheralization With virus delivered as PFC suspension (right panel (c)), β-gal expression is seen in more global regions of the parenchyma. Based on the location and morphology, these cells appear to be type II cells. Panel D displays additional examples of whole mounts of lungs from mice transduced with rAd-CMVLacZ ( viral particles) administered in saline alone, by saline followed by a chase of PP2:PP9 (10 mL/kg), or as a rAd/PP2:PP9 suspension.