Optimum Therapeutics LLC, The Ohio State University Science Tech Village, Columbus, 43212, USA.
AAPS J. 2010 Dec;12(4):492-503. doi: 10.1208/s12248-010-9210-4. Epub 2010 Jun 11.
RNA interference is a naturally occurring endogenous regulatory process where short double-stranded RNA causes sequence-specific posttranscriptional gene silencing. Small interference RNA (siRNA) represents a promising therapeutic strategy. Clinical evaluations of siRNA therapeutics in locoregional treatment settings began in 2004. Systemic siRNA therapy is hampered by the barriers for siRNA to reach their intended targets in the cytoplasm and to exert their gene silencing activity. The three goals of this review were to provide an overview of (a) the barriers to siRNA delivery, from the perspectives of physicochemical properties of siRNA, pharmacokinetics and biodistribution, and intracellular trafficking; (b) the non-viral siRNA carriers including cell-penetrating peptides, polymers, dendrimers, siRNA bioconjugates, and lipid-based siRNA carriers; and (c) the current status of the clinical trials of siRNA therapeutics.
RNA 干扰是一种自然发生的内源性调节过程，其中短双链 RNA 导致序列特异性转录后基因沉默。小干扰 RNA（siRNA）代表了一种有前途的治疗策略。2004 年开始在局部治疗环境中对 siRNA 治疗进行临床评估。系统的 siRNA 治疗受到阻碍，因为 siRNA 难以到达细胞质中的靶标并发挥其基因沉默活性。本综述的三个目标是提供（a）siRNA 递送至靶细胞的障碍的概述，包括 siRNA 的理化性质、药代动力学和生物分布以及细胞内转运；（b）非病毒 siRNA 载体，包括穿透肽、聚合物、树枝状聚合物、siRNA 生物缀合物和基于脂质的 siRNA 载体；和（c）siRNA 治疗的临床试验的现状。
