Silence Therapeutics AG, Robert-Rössle-Str. 10, 13125 Berlin, Germany.
Microvasc Res. 2010 Sep;80(2):286-93. doi: 10.1016/j.mvr.2010.02.002. Epub 2010 Feb 6.
RNA interference (RNAi) has become an indispensable tool for loss of function analysis in today's basic cell biological research, and is currently being utilized for developing novel therapeutic methods. Systemic administration of synthetic small interfering RNA (siRNA) into the bloodstream is a feasible route for targeting the vascular endothelium or peripheral blood cells. The vascular endothelium can be considered an organ by itself, involved in many pathophysiological processes. Here, we aim to summarize current strategies of using RNAi for analysis of gene function in endothelial (in vitro loss-of-function analysis) and of exploiting RNAi for therapeutic purposes in order to suppress disrupted gene expression ("RNAi therapeutics"). With respect to the latter, we will summarize recent experimental concepts as well as ongoing therapeutic applications of RNAi mediated suppression of gene expression modulating angiogenic processes in cancer and retinopathies. We will further discuss the opportunities, prospects, challenges and potential fallbacks as well as the present strategies for the realization of "RNAi therapeutics" in combating vascular diseases.
RNA 干扰 (RNAi) 已成为当今基础细胞生物学研究中功能丧失分析不可或缺的工具，并且目前正在被用于开发新的治疗方法。将合成的小干扰 RNA (siRNA) 全身性给药到血液中是靶向血管内皮或外周血细胞的可行途径。血管内皮本身可以被视为一个器官，参与许多病理生理过程。在这里，我们旨在总结目前使用 RNAi 分析内皮细胞中基因功能的策略（体外功能丧失分析）以及利用 RNAi 进行治疗以抑制基因表达失调的策略（“RNAi 治疗学”）。关于后者，我们将总结最近的实验概念以及正在进行的 RNAi 介导的基因表达抑制治疗应用，这些应用可以调节癌症和视网膜病变中的血管生成过程。我们将进一步讨论在对抗血管疾病时实现“RNAi 治疗学”的机会、前景、挑战和潜在障碍以及当前策略。
