Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, University of Aarhus, Aarhus, Denmark.
Adv Drug Deliv Rev. 2012 Dec;64(15):1717-29. doi: 10.1016/j.addr.2012.07.004. Epub 2012 Jul 16.
Small interfering RNA (siRNA) that silence genes by the process of RNA interference offers a new therapeutic modality for disease treatment. Polycation-based nanoparticles termed polyplexes have been developed to maximise extracellular and intracellular siRNA delivery, a key requirement for enabling the clinical translation of RNAi-based drugs. Medical applications are dependent on safety; therefore, detailed investigation into potential toxicity to the cell or organism is required. This review addresses potential adverse effects arising from cellular and tissue interactions, immune stimulation and altered gene expression that can be associated with the assembled polyplex or the polycation and siRNA component parts. A greater understanding of the cellular mechanisms involved allows design-based solutions for rationale development of safe, effective and clinically relevant polyplex-based RNAi drugs.
小干扰 RNA（siRNA）通过 RNA 干扰过程沉默基因，为疾病治疗提供了一种新的治疗方式。基于聚阳离子的纳米颗粒被称为聚合物，已被开发用于最大限度地提高细胞外和细胞内 siRNA 的递送，这是实现基于 RNAi 的药物临床转化的关键要求。医学应用依赖于安全性；因此，需要对细胞或生物体的潜在毒性进行详细调查。本综述讨论了与组装的聚合物或聚阳离子和 siRNA 组成部分相关的细胞和组织相互作用、免疫刺激和改变的基因表达引起的潜在不良影响。更深入地了解所涉及的细胞机制可以为合理开发安全、有效和临床相关的聚合物基 RNAi 药物提供基于设计的解决方案。
