Sené C, Bout A, Imler J L, Schultz H, Willemot J M, Hennebel V, Zurcher C, Valerio D, Lamy D, Pavirani A
Transgene S.A., Strasbourg, France.
Hum Gene Ther. 1995 Dec;6(12):1587-93. doi: 10.1089/hum.1995.6.12-1587.
At present, it is conceivable that gene therapy of the cystic fibrosis airway epithelium is possible using the direct transfer of a functional human cystic fibrosis transmembrane conductance regulator (CFTR) gene to a wide variety of patients' tracheo-bronchial cells. Here we describe a novel approach (aerosolization) to deliver a replication-deficient adenovirus carrying the CFTR gene (Ad.CFTR) to the airways. Results obtained in vitro and in Rhesus monkeys suggest that the delivery of recombinant adenovirus as an aerosol is feasible and is not associated with severe toxicity after single or double administration depending on the Ad.CFTR dose. This study supports the concept of aerosolization as a delivery method for adenovirus-mediated lung gene therapy.
目前，可以想象，通过将功能性人类囊性纤维化跨膜传导调节因子（CFTR）基因直接转移到多种患者的气管支气管细胞中，对囊性纤维化气道上皮进行基因治疗是可行的。在此，我们描述了一种将携带CFTR基因的复制缺陷型腺病毒（Ad.CFTR）递送至气道的新方法（雾化）。体外和恒河猴实验获得的结果表明，雾化递送重组腺病毒是可行的，并且根据Ad.CFTR剂量，单次或两次给药后均无严重毒性。本研究支持雾化作为腺病毒介导的肺部基因治疗递送方法的概念。
