Kuwait University, Health Sciences Centre, Department of Pharmacology and Toxicology, Faculty of Medicine, PO Box 24923, Safat 13110, Kuwait.
Expert Opin Drug Metab Toxicol. 2010 Nov;6(11):1347-62. doi: 10.1517/17425255.2010.518611. Epub 2010 Oct 7.
siRNAs may serve as novel nanomedicines for sequence-specific gene silencing in the clinic. However, delivering siRNA to targeted tissue or cells remains a challenge. An appropriate delivery nanosystem such as cationic polymers or liposomes is required for effective gene silencing with siRNA in vivo but the available drug delivery vectors are not all biologically inert.
A combination of highly focused and comprehensive literature searches to identify any relevant reports using Medline (from 1950 to 7 April 2010) through the OVID system.
Using cationic delivery nanosystems as examples, this review article highlights the importance of undertaking toxicogenomics studies - the application of transcription profiling to toxicology - to acquire gene expression signatures of siRNA delivery systems so as to determine and/or predict their impact on gene silencing activity and specificity. Such nanotoxicological information will be important for the optimal selection of siRNA-delivery system combinations in the many proposed clinical applications of RNA interference.
Cationic delivery nanosystems can elicit multiple gene expression changes in cells that may contribute to the 'off-target' effects of siRNAs and/or modulate their pharmacological activity. Thus, selection of delivery systems for siRNA applications should be based on both their delivery enhancing capability and toxicogenomics.
siRNA 可作为一种新型的纳米药物，用于临床中特定序列的基因沉默。然而，将 siRNA 递送至靶向组织或细胞仍然是一个挑战。体内有效的 siRNA 基因沉默需要合适的递药纳米系统，如阳离子聚合物或脂质体，但现有的药物递药载体并非完全没有生物活性。
通过 OVID 系统在 Medline（从 1950 年到 2010 年 4 月 7 日）上进行了高度集中和全面的文献检索，以确定任何相关报道。
本文以阳离子递药纳米系统为例，强调了进行毒代基因组学研究的重要性——将转录谱分析应用于毒理学，以获得 siRNA 递药系统的基因表达特征，从而确定和/或预测它们对基因沉默活性和特异性的影响。这种纳米毒理学信息对于 RNA 干扰的许多临床应用中，siRNA 递药系统组合的最佳选择非常重要。
阳离子递药纳米系统可引起细胞内的多个基因表达变化，这些变化可能导致 siRNA 的“脱靶”效应，或调节其药理学活性。因此，siRNA 应用的递药系统选择应基于其递药增强能力和毒代基因组学。
