AEROSOL AND INTRAVENOUS TRANSFECTION OF HUMAN ALPHA-1-ANTITRYPSIN GENE TO LUNGS OF RABBITS
AEROSOL AND INTRAVENOUS TRANSFECTION OF HUMAN ALPHA-1-ANTITRYPSIN GENE TO LUNGS OF RABBITS
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DOI：
10.1165/ajrcmb.10.1.8292378
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发表时间：
1994-01-01
影响因子：
6.4
通讯作者：
BRIGHAM, KL
中科院分区：
文献类型：
--
作者：
CANONICO, AE;CONARY, JT;BRIGHAM, KL
体内基因转移到肺部是可能的，可以通过静脉或呼吸道给药途径。将含有重组人α1-抗胰蛋白酶(Halpha1AT)基因和巨细胞病毒启动子的阳离子脂质体复合的重组质粒静脉或气雾化给新西兰大白兔。这两种给药途径都成功地导入和表达了halpha1AT基因。至少7天后检测Halpha1AT基因和蛋白的表达。免疫组织化学染色显示，静脉给药后肺内皮细胞、雾化吸入后肺泡上皮细胞和任一途径的呼吸道上皮细胞均有Halpha1AT蛋白表达。静脉注射放射性标记物后，放射自显影显示内皮细胞，特别是动脉分叉处和肺泡水平上有质粒的定位。用于肺部基因治疗的质粒-脂质体递送系统可能允许通过选择递送途径将DNA靶向于肺细胞亚群，并可能允许基因治疗在急慢性疾病中的广泛应用。
In vivo gene transfer to the lungs is possible either by an intravenous or an airway route of administration. A plasmid containing the recombinant human alpha1-antitrypsin (halpha1AT) gene and a cytomegalovirus promoter complexed to cationic liposomes was given either intravenously or by aerosol to New Zealand White rabbits. Both routes of administration resulted in successful transfection and expression of the halpha1AT gene. halpha1AT mRNA and protein were detected for at least 7 days. Immunohistochemical staining showed halpha1AT protein in the pulmonary endothelium following intravenous administration, in alveolar epithelial cells following aerosol administration, and in the airway epithelium by either route. After intravenous injection of radiolabeled plasmids, autoradiographs showed localization of plasmid in endothelial cells, especially at arterial bifurcations, and at die alveolar level. A plasmid-liposome delivery system for gene therapy to the lungs may permit targeting of the DNA to subsets of lung cells by selection of the route of delivery and may permit a broad application of gene therapy to acute as well as chronic diseases.