以两亲性细胞膜穿透肽为基础的siRNA递送策略

An Amphipathic Cell-penetrating Peptide-Based Strategy for si RNA Delivery

小干扰RNA(si RNA)的发展给针对病理障碍特异性基因的靶向治疗带来了巨大的希望。然而,细胞膜对带负电荷分子的低渗透性,细胞对si RNA的摄取能力差,成为了si RNA临床应用的主要障碍。虽然学者们提出了一系列si RNA递送的方法,但是截止到目前,仍没有递送si RNA的通用方法。细胞膜穿透肽(cell-penetrating peptides,CPPs)的发现为si RNA非侵袭性的进入细胞提供了一种非常有前景的运载工具,已被成功地应用于治疗性si RNA分子的体内和体外实验的递送。最近,一种新的以两亲性CPPs为基础的si RNA递送系统-CADY(a secondary amphipathic peptide,Ac-GLWRALWRLLRSLWRLLWRA-cysteamide)受到了高度关注,它能与si RNA形成稳定的非共价复合物,并在原代和悬浮细胞系中高效地递送si RNA,具有极高的应用前景。

The development of short-interfering RNA（si RNA） has provided great hope for therapeutic targeting of specific genes responsible for pathological disorders. However, the poor cellular uptake of si RNA together with the low permeability of the cell membrane to negatively charged molecules, remain major obstacles to clinical development. So far there is no universal method for si RNA delivery as they all present some limitations. Some strategies have been proposed to improve the delivery of synthetic si RNAs in both cultured cells and in vivo. Cell-penetrating peptides（CPPs） constitute very promising tools for non-invasive cellular import of si RNA and non-covalent CPPs-based strategies have been successfully applied for in vitro and in vivo delivery of therapeutic si RNA molecules. A new peptide-based system, CADY, for efficient delivery of si RNA in both primary and suspension cell lines has been described recently. CADY is a secondary amphipathic peptide able to form stable non-covalent complexes with si RNA and to improve their adherent and suspension cell lines uptake, which shows high potential in clinical use.