An approach for treating the hepatobiliary disease of cystic fibrosis by somatic gene transfer.
An approach for treating the hepatobiliary disease of cystic fibrosis by somatic gene transfer.
复制标题
DOI：
10.1073/pnas.90.10.4601
复制
发表时间：
1993-05
影响因子：
11.1
通讯作者：
Yiping Yang;S. Raper;J. Cohn;J. Engelhardt;J. M. Wilson
中科院分区：
文献类型：
--
作者：
Yiping Yang;S. Raper;J. Cohn;J. Engelhardt;J. M. Wilson
囊性纤维化（CF）是一种上皮细胞离子转运的遗传性疾病，与肺、胰腺和肝脏等多器官系统的病理有关。随着CF肺部表现治疗的改善，CF肝脏疾病的管理在成人患者中变得越来越重要。本报告描述了一种通过体细胞基因转移治疗CF肝病的方法。原位杂交和免疫细胞化学分析表明，内源性CFTR（囊性纤维化跨膜传导调节因子）基因主要在肝内胆道上皮细胞中表达。将表达lacZ或人CFTR的重组腺病毒经胆总管逆行注入胆道，在体内将重组基因特异性靶向胆道上皮。建立了在体内几乎所有肝内胆管细胞中实现重组基因表达的条件。在实验期间，较小的胆管中表达持续21天。这些研究表明，通过基因重组胆道CFTR表达来预防CF肝病可能是可行的，这是一种临床可行的方法。
Cystic fibrosis (CF) is an inherited disease of epithelial cell ion transport that is associated with pathology in multiple organ systems, including lung, pancreas, and liver. As treatment of the pulmonary manifestations of CF has improved, management of CF liver disease has become increasingly important in adult patients. This report describes an approach for treating CF liver disease by somatic gene transfer. In situ hybridization and immunocytochemistry analysis of rat liver sections indicated that the endogenous CFTR (cystic fibrosis transmembrane conductance regulator) gene is primarily expressed in the intrahepatic biliary epithelial cells. To specifically target recombinant genes to the biliary epithelium in vivo, recombinant adenoviruses expressing lacZ or human CFTR were infused retrograde into the biliary tract through the common bile duct. Conditions were established for achieving recombinant gene expression in virtually all cells of the intrahepatic bile ducts in vivo. Expression persisted in the smaller bile ducts for the duration of the experiment, which was 21 days. These studies suggest that it may be feasible to prevent CF liver disease by genetically reconstituting CFTR expression in the biliary tract, using an approach that is clinically feasible.