Weirauch Ulrike, Gutsch Daniela, Höbel Sabrina, Aigner Achim
Rudolf-Boehm-Institute for Pharmacology and Toxicology, Clinical Pharmacology University of Leipzig, Leipzig, Germany.
Methods Mol Biol. 2013;1049:443-65. doi: 10.1007/978-1-62703-547-7_34.
RNA interference (RNAi) is a naturally occurring, powerful mechanism for gene silencing, based on the cleavage of a given target mRNA. It relies on small interfering RNAs (siRNAs) in the cell. Being similar in structure, microRNAs (miRNAs) are important regulators of gene expression which mainly act by blocking mRNA translation. In cancer, certain miRNAs have been found to be pathologically downregulated. The therapeutic application of siRNAs or miRNAs for the induction of RNAi or miRNA replacement, respectively, relies on their efficient delivery through a non-viral formulation. Complexation of siRNAs/miRNAs in polymeric nanoparticles based on polyethylenimines (PEIs) offers protection against degradation, delivery to the target site, cellular uptake, and intracellular release. This chapter provides protocols for therapeutic gene silencing and miRNA replacement therapy, based on PEI complexes for in vitro and in vivo use.
RNA干扰（RNAi）是一种基于特定靶mRNA切割的自然发生的强大基因沉默机制。它依赖于细胞中的小干扰RNA（siRNA）。微小RNA（miRNA）在结构上与之相似，是基因表达的重要调节因子，主要通过阻断mRNA翻译发挥作用。在癌症中，已发现某些miRNA在病理上表达下调。分别用于诱导RNAi或进行miRNA替代的siRNA或miRNA的治疗应用，依赖于它们通过非病毒制剂的有效递送。基于聚乙烯亚胺（PEI）的聚合物纳米颗粒中siRNA/miRNA的复合，可提供抗降解保护、递送至靶位点、细胞摄取和细胞内释放。本章提供了基于PEI复合物用于体外和体内使用的治疗性基因沉默和miRNA替代疗法的方案。
