Canonico A E, Plitman J D, Conary J T, Meyrick B O, Brigham K L
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
J Appl Physiol (1985). 1994 Jul;77(1):415-9. doi: 10.1152/jappl.1994.77.1.415.
The safety aspects of human gene therapy are of paramount importance in developing an ideal system for gene transfer. Lipofection using DNA in the form of a plasmid has been shown to successfully transfect the lungs when administered either intravenously or by aerosol. We have shown that repeated intravenous or aerosol administration of a plasmid containing the recombinant human alpha 1-antitrypsin gene and a cytomegalovirus promoter complexed to cationic liposomes results in no adverse effects on pulmonary histology, lung compliance, lung resistance, or alveolar-arterial oxygen gradient. Immunohistochemistry and Western blot analysis confirm successful gene transfer using this delivery system. We conclude that plasmids complexed to cationic liposomes may be a safe and efficacious delivery system for in vivo gene transfer to the lungs. Using this delivery system, in vivo gene therapy to the lungs can be achieved by either intravenous or aerosol administration of the transgene.
在开发理想的基因转移系统过程中，人类基因治疗的安全性至关重要。已证实，以质粒形式使用DNA进行脂质体转染，无论是静脉注射还是通过气雾剂给药，都能成功转染肺部。我们已经表明，将含有重组人α1-抗胰蛋白酶基因和巨细胞病毒启动子并与阳离子脂质体复合的质粒反复静脉注射或通过气雾剂给药，对肺组织学、肺顺应性、肺阻力或肺泡-动脉氧梯度均无不良影响。免疫组织化学和蛋白质印迹分析证实了使用该递送系统成功进行了基因转移。我们得出结论，与阳离子脂质体复合的质粒可能是一种安全有效的用于肺部体内基因转移的递送系统。使用该递送系统，通过静脉注射或气雾剂给药转基因，均可实现对肺部的体内基因治疗。
