Kidney-selective gene transfection using anionic bubble lipopolyplexes with renal ultrasound irradiation in mice
Kidney-selective gene transfection using anionic bubble lipopolyplexes with renal ultrasound irradiation in mice
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DOI：
10.1016/j.nano.2014.06.009
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发表时间：
2014-11-01
影响因子：
5.4
通讯作者：
Hashida, Mitsuru
中科院分区：
文献类型：
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作者：
Kurosaki, Tomoaki;Kawakami, Shigeru;Hashida, Mitsuru
本研究评估了一种新的超声（US）反应性基因传递载体，泡脂多丛，将基因传递到肾脏的能力。泡脂多丛在肾小管中表现出高度选择性的基因表达，但仅在肾用US照射后才表现出来。然而，这些泡状脂质多丛并没有增加肾损伤生物标志物的表达，包括血尿素氮、血清肌酐、肾损伤分子-1 mRNA和聚簇蛋白mRNA，也没有引起肾脏的任何组织病理学异常。此外，含有CMV早期增强子/鸡β -肌动蛋白启动子的pDNA延长了肾泡脂多丛基因表达42天。这种新的肾脏基因传递方法，即在转染泡脂多丛后，对肾脏进行US照射，导致小鼠的细胞选择性、高水平和长期的基因表达，而不损伤肾脏，可能在未来的患者治疗中有应用。来自临床编辑：本研究展示了一种新的基因传递到肾脏的方法，利用超声照射后肾小管中的气泡导致高选择性基因表达。在研究的啮齿动物模型中，没有证据表明使用这种新型给药系统会造成肾脏损害。(C) 2014爱思唯尔公司版权所有。
This study assessed the ability of a new ultrasound (US) responsive gene delivery carrier, bubble lipopolyplexes, to deliver genes to the kidneys. The bubble lipopolyplexes showed highly selective gene expression in kidney tubules, but only after renal irradiation with US. These bubble lipopolyplexes, however, did not increase the expression of biomarkers of kidney injury, including blood urea nitrogen, serum creatinine, kidney injury molecule-1 mRNA, and clusterin mRNA, or induce any histopathological abnormalities in the kidney. Furthermore, pDNA containing CMV early enhancer/chicken beta-actin promoter prolonged gene expression by the bubble lipopolyplexes in the kidney for 42 days. This novel renal gene delivery method, in which transfection of bubble lipopolyplexes was followed by US irradiation of the kidneys, resulting in cell-selective, high, and long-term gene expression without renal injury in mice, may have future applications in patient treatment.From the Clinical Editor: This study demonstrates a novel gene delivery method to the kidneys, utilizing bubble resulting in highly selective gene expression in renal tubules after ultrasound irradiation. In the studied rodent model, there was no evidence for renal damage using this novel delivery system. (C) 2014 Elsevier Inc. All rights reserved.