综述: 细胞穿透肽及其结构改造在siRNA传递中的应用

小RNA药物应用于临床的主要技术瓶颈在于如何高效、低毒地将小RNA分子传递到它发挥功能的场所．基于细胞穿透肽在小RNA透皮给药的临床应用中所取得的进展，本文系统评述了近年来细胞穿透肽在小RNA的体内、体外传递方面的研究动态，分析了细胞穿透肽的结构改造对肽/小RNA复合物转染进入细胞发挥功能的影响，展望了细胞穿透肽作为小RNA的体内药物传递载体的发展方向．

Review: The Effects of Cell Penetrating Peptides Structure Modification on Their siRNA Delivery Function in vitro and in vivo

The less of high efficient carriers to deliver siRNA drugs into their targeted tissues/cells with less toxicity are the major obstacles of siRNA pharmaceuticals in clinic application. The recent advance of siRNA delivery research based on cell-penetrating peptides (CPPs) in clinic opened the way of siRNA techniques for therapeutic application (Yi et al., Mol Ther (2011)19, 362-371). CPPs are short amphipathic and cationic peptides that are rapidly internalized across cell membranes. They can be used to deliver molecular cargos, such as imaging agents (fluorescent dyes and quantum dots), drugs, liposomes, peptide/protein, oligonucleotide/DNA/RNA, nanoparticles and bacteriophage into cells. The mechanism of cellular uptake and subsequent processing still remains controversial. It is now clear that CPP can mediate intracellular delivery via both endocytic and non-endocytic pathways. In this review, we discuss potential functions of CPPs, especially in structure modified CPPs for small RNA delivery in vitro and in vivo, highlighting their powerful promise for clinical efficacy.