Perfluorochemical Liquid-Adenovirus Suspensions Enhance Gene Delivery to the Distal Lung

The Cardiopulmonary Research Institute and Departments of Medicine and Pediatrics, SUNY Stony Brook School of Medicine, Winthrop University Hospital, Mineola, NY 11507, USA.
Pulmonary Medicine 08/2011; 2011(4):918036. DOI: 10.1155/2011/918036
Source: PubMed


WE COMPARED LUNG DELIVERY METHODS OF RECOMBINANT ADENOVIRUS (RAD): (1) rAd suspended in saline, (2) rAd suspended in saline followed by a pulse-chase of a perfluorochemical (PFC) liquid mixture, and (3) a PFC-rAd suspension. Cell uptake, distribution, and temporal expression of rAd were examined using A549 cells, a murine model using luciferase bioluminescence, and histological analyses. Relative to saline, a 4X increase in transduction efficiency was observed in A549 cells exposed to PFC-rAd for 2-4 h. rAd transgene expression was improved in alveolar epithelial cells, and the level and distribution of luciferase expression when delivered in PFC-rAd suspensions consistently peaked at 24 h. These results demonstrate that PFC-rAd suspensions improve distribution and enhance rAd-mediated gene expression which has important implications in improving lung function by gene therapy.

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    • "This is in large part due to a propulsive effect in which the immiscible PFC liquids are administered immediately after aqueous vector solutions and result in improved penetration and distribution throughout the airways. Some formulations of PFC liquids allow some degree of mixing with aqueous vector solutions, and these suspensions may also improve distribution of transgene expression in lung epithelium (Kazzaz et al., 2011). PFC liquids also have other effects that enhance gene expression. "
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