Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University.
Division of Nephrology, First Department of Integrated Medicine, Saitama Medical Center, Jichi Medical University;
J Vis Exp. 2022 May 10(183). doi: 10.3791/63302.
microRNSa (miRNAs), small noncoding RNAs (21-25 bases) that are not translated into proteins, inhibit lots of target messenger RNAs (mRNAs) by destabilizing and inhibiting their translation in various kidney diseases. Therefore, alternation of miRNA expression by exogenous artificially synthesized miRNA mimics is a potentially useful treatment option for inhibiting the development of many kidney diseases. However, because serum RNAase immediately degrades systematically administered exogenous miRNA mimics in vivo, delivery of miRNA to the kidney remains a challenge. Therefore, vectors that can protect exogenous miRNA mimics from degradation by RNAase and significantly deliver them to the kidney are necessary. Many studies have used viral vectors to deliver exogenous miRNA mimics or inhibitors to the kidney. However, viral vectors may cause an interferon response and/or genetic instability. Therefore, the development of viral vectors is also a hurdle for the clinical use of exogenous miRNA mimics or inhibitors. To overcome these concerns regarding viral vectors, we developed a nonviral vector method to deliver miRNA mimics to the kidney using tail vein injection of polyethylenimine nanoparticles (PEI-NPs), which led to significant overexpression of target miRNAs in several mouse models of kidney disease.
微小 RNA（miRNAs）是一种非编码的小 RNA（21-25 个碱基），不能翻译成蛋白质，在各种肾脏疾病中通过使靶信使 RNA（mRNA）不稳定和抑制其翻译来抑制大量靶 mRNA。因此，通过外源性人工合成的 miRNA 模拟物改变 miRNA 的表达是抑制许多肾脏疾病发展的一种潜在有用的治疗选择。然而，由于血清 RNA 酶会立即在体内降解系统给予的外源性 miRNA 模拟物，因此 miRNA 向肾脏的传递仍然是一个挑战。因此，需要能够保护外源性 miRNA 模拟物免受 RNA 酶降解并将其有效递送至肾脏的载体。许多研究已经使用病毒载体将外源性 miRNA 模拟物或抑制剂递送至肾脏。然而，病毒载体可能会引起干扰素反应和/或遗传不稳定性。因此，病毒载体的发展也是外源性 miRNA 模拟物或抑制剂临床应用的一个障碍。为了克服对病毒载体的担忧，我们开发了一种非病毒载体方法，通过尾静脉注射聚乙烯亚胺纳米颗粒（PEI-NPs）将 miRNA 模拟物递送至肾脏，这导致几种肾脏疾病的小鼠模型中的靶 miRNA 显著过表达。
