Kazzaz Jeffrey A, Strayer Marlene S, Wu Jichuan, Malone Daniel J, Koo Hshi-Chi, Shaffer Thomas H, Davis Jonathan M, Strayer David S, Wolfson Marla R
The Cardiopulmonary Research Institute and Departments of Medicine and Pediatrics, SUNY Stony Brook School of Medicine, Winthrop University Hospital, Mineola, NY 11507, USA.
Pulm Med. 2011;2011:918036. doi: 10.1155/2011/918036. Epub 2011 Aug 18.
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.
我们比较了重组腺病毒（rAd）的肺部递送方法：（1）悬浮于盐水中的rAd；（2）悬浮于盐水中的rAd，随后进行全氟化合物（PFC）液体混合物的脉冲追踪；（3）PFC-rAd悬浮液。使用A549细胞、利用荧光素酶生物发光的小鼠模型以及组织学分析，检测了rAd的细胞摄取、分布和瞬时表达。相对于盐水，暴露于PFC-rAd 2-4小时的A549细胞的转导效率提高了4倍。rAd转基因表达在肺泡上皮细胞中得到改善，以PFC-rAd悬浮液递送时，荧光素酶表达的水平和分布在24小时时始终达到峰值。这些结果表明，PFC-rAd悬浮液改善了分布并增强了rAd介导的基因表达，这对通过基因治疗改善肺功能具有重要意义。
