Case Western Reserve University, Biomedical Engineering, 309 Wickenden, 10900 Euclid Avenue, Cleveland, OH, USA.
Chemistry. 2011 Mar 7;17(11):3054-62. doi: 10.1002/chem.201003144. Epub 2011 Feb 21.
Short interfering RNA (siRNA) functions directly in the cytoplasm, where it is assembled into an RNA-induced silencing complex (RISC). The localized delivery of siRNA to a specific site in vivo is highly challenging. There are many disease states in which a systemic effect of RNAi may be desirable; some examples include non-localized cancers, HIV, neurodegenerative diseases, respiratory viruses, and heart and vascular disease. In this Concept, we will focus on the localized delivery of siRNA to a target site using various delivery modalities. In certain tissues, such as the eye, central nervous system and lung, it has been demonstrated that a simple injection of naked siRNA will silence gene expression specifically in that tissue. To achieve local gene silencing in other tissues, a variety of approaches have been pursued to help stabilize the siRNA and facilitate uptake; they include chemical modification of the siRNA or complexation within liposomes or polymers to form nanoparticles. Recently, the use of macroscopic biomaterial scaffolds for siRNA delivery has been reported, and although there is still significant work to be done in this area to optimize the delivery systems, it is an important area of research that offers the potential for having great impact on the field of siRNA delivery.
短干扰 RNA（siRNA）在细胞质中直接发挥作用，在细胞质中，它被组装成 RNA 诱导沉默复合物（RISC）。将 siRNA 递送到体内特定部位具有很大的挑战性。有许多疾病状态可能需要 RNAi 的全身作用；一些例子包括非局部性癌症、HIV、神经退行性疾病、呼吸道病毒以及心脏和血管疾病。在本概念中，我们将重点讨论使用各种递药方式将 siRNA 递送到靶部位。在某些组织中，如眼睛、中枢神经系统和肺部，已经证明简单地注射裸露的 siRNA 可以特异性地沉默该组织中的基因表达。为了在其他组织中实现局部基因沉默，已经尝试了多种方法来帮助稳定 siRNA 并促进摄取；它们包括 siRNA 的化学修饰或包封在脂质体或聚合物中以形成纳米颗粒。最近，已经报道了使用宏观生物材料支架进行 siRNA 递药的方法，尽管在该领域还有大量工作要做以优化递药系统，但这是一个重要的研究领域，有可能对 siRNA 递药领域产生重大影响。
