Clinical Pharmacology, Faculty of Medicine, Rudolf-Boehm-Institute of Pharmacology and Toxicology, University Leipzig, Leipzig, Germany.
Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2013 Sep-Oct;5(5):484-501. doi: 10.1002/wnan.1228. Epub 2013 May 29.
The discovery of RNA interference (RNAi) as a naturally occurring mechanism for gene knockdown has attracted considerable attention toward the use of small interfering RNAs (siRNAs) for therapeutic purposes. Likewise, microRNAs (miRNAs) have emerged as important cellular regulators of gene expression, and their pathological underexpression allows for novel therapeutic strategies ('miRNA replacement therapy'). To address issues related to the instability, charge, and molecular weight of small RNA molecules, nanoparticle formulations have been explored for their in vivo application. Polyethylenimines (PEIs) are positively charged, linear, or branched polymers that are able to form nanoscale complexes with small RNAs, leading to RNA protection, cellular delivery, and intracellular release. This review highlights the important properties of various PEIs with regard to their use for in vivo RNA delivery. PEI modifications for increased efficacy, altered pharmacokinetic properties, improved biocompatibility and, upon covalent coupling of ligands, targeted delivery are described. An overview of various modified PEIs and a comprehensive list of representative studies using PEI-based siRNA or miRNA delivery in vivo are given.
RNA 干扰 (RNAi) 的发现作为一种自然发生的基因敲低机制，引起了人们对小干扰 RNA (siRNA) 用于治疗目的的极大关注。同样，microRNAs (miRNAs) 已成为基因表达的重要细胞调节剂，其病理性表达不足为新的治疗策略提供了可能（“miRNA 替代疗法”）。为了解决小 RNA 分子的不稳定性、电荷和分子量等问题，人们探索了纳米颗粒制剂在体内的应用。聚乙二亚胺 (PEI) 是带正电荷的线性或支化聚合物，能够与小 RNA 形成纳米级复合物，从而实现 RNA 保护、细胞递送和细胞内释放。本综述重点介绍了各种 PEI 的重要性质，及其在体内 RNA 递送中的应用。描述了用于提高功效、改变药代动力学特性、提高生物相容性以及通过配体的共价偶联进行靶向递送的 PEI 修饰。概述了各种修饰的 PEI 以及使用基于 PEI 的 siRNA 或 miRNA 在体内进行递送的代表性研究的综合列表。
