siRNA及其运载系统研究进展

小干扰RNA （small interfering RNA，siRNA）通过基因干扰技术进行有针对性的基因沉默，其控制目标基因表达的能力为基因治疗癌症和遗传性疾病提供了新的希望。但siRNA的药理性能很低，如血清稳定性低、脱靶、先天免疫反应，为临床治疗提供了一个挑战。由于负离子性能和刚性结构致使siRNA难以穿透细胞膜，因此，构建安全、稳定、高效的siRNA运载系统将siRNA运载到靶细胞的细胞质是至关重要的。作者综述了几种可增强体内外细胞摄取和靶基因沉默的广泛、发达的非病毒性siRNA运载系统，并讨论了它们的特点和进行siRNA治疗用于临床应用的机会，以期为今后siRNA的研究与临床应用奠定基础。

Research Progress on Small Interfering RNA and Its Delivery Systems

Small interfering RNA (siRNA) has proved to be a powerful tool for target-specific gene silencing via RNA interference (RNAi). Its ability to control targeted gene expression gives new hope to gene therapy as a treatment for cancers and genetic diseases. However,siRNA shows poor pharmacological properties, such as low serum stability,off-targeting, and innate immune responses, which present a significant challenge for clinical applications.In addition, siRNA cannot cross the cell membrane for siRNA activity because of its anionic property and stiff structure.Therefore, the development of a safe,stable,and efficient system for the delivery of siRNA therapeutics into the cytoplasm of targeted cells is crucial. Several nanoparticle platforms for siRNA delivery have been developed to overcome the major hurdles facing the therapeutic uses of siRNA. This review covers a broad spectrum of non-viral siRNA delivery systems developed for enhanced cellular uptake and targeted gene silencing in vitro and in vivo, and discusses their characteristics and opportunities for clinical applications of therapeutic siRNA,in order to lay a good foundation for the later research.