Mukai Hidefumi, Kawakami Shigeru, Hashida Mitsuru
Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Yakugaku Zasshi. 2008 Nov;128(11):1577-86. doi: 10.1248/yakushi.128.1577.
The kidney is one of the most important organs that play a crucial role in homeostasis and, therefore, congenital or acquired renal dysfunction causes refractory diseases, i.e., Alport's syndrome, Fabry's disease, diabetic nephropathy, IgA nephropathy, kidney cancer, transplant glomerulopathy. Nucleic acid transfection technology to the kidney is indispensable for the progress of biomedical research and the realization of gene therapy and nucleic acid drug for renal diseases. Control of renal nucleic acid transfection was difficult because of the structural complexity; however, the study of recombinant virus, synthetic carrier and physical force-mediated nucleic acid transfection to the kidney has advanced. Recombinant virus and synthetic carrier-mediated methods require long-term block of the blood or urinary flow for efficient transfection of nucleic acid because of the rich blood flow of the kidney. In contrast, physical force-mediated methods that transfect with nucleic acid via transient membrane permeability do not apprehend ischemia-reperfusion injury and, therefore, may be beneficial for nucleic acid transfection to the kidney. In this article, we collect the information of therapeutic gene, target molecule of the nucleic acid drug and target cells for renal diseases and structural property of the kidney from the point of view of nucleic acid transfection. Additively, current status of nucleic acid transfection technology to the kidney is reviewed.
肾脏是在体内平衡中发挥关键作用的最重要器官之一,因此,先天性或后天性肾功能障碍会引发难治性疾病,即阿尔波特综合征、法布里病、糖尿病肾病、IgA肾病、肾癌、移植性肾小球病。肾脏的核酸转染技术对于生物医学研究的进展以及肾脏疾病基因治疗和核酸药物的实现不可或缺。由于肾脏结构复杂,对其进行核酸转染的控制较为困难;然而,针对肾脏的重组病毒、合成载体和物理力介导的核酸转染研究已经取得了进展。由于肾脏血流丰富,重组病毒和合成载体介导的方法需要长期阻断血流或尿流才能实现核酸的高效转染。相比之下,通过瞬时膜通透性进行核酸转染的物理力介导方法不会引发缺血再灌注损伤,因此可能有利于肾脏的核酸转染。在本文中,我们从核酸转染的角度收集了治疗基因、肾脏疾病核酸药物的靶分子和靶细胞以及肾脏结构特性的信息。此外,还综述了肾脏核酸转染技术的现状。