Department of Advanced Clinical Science and Therapeutics, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo, 113-8655 Japan.
J Am Coll Cardiol. 2010 Mar 2;55(9):904-13. doi: 10.1016/j.jacc.2009.09.054.
The purpose of this study was to investigate the efficiency of small interfering ribonucleic acid (siRNA) in murine arteries. We transfected it using a nonviral ultrasound-microbubble-mediated in vivo gene delivery system.
siRNA is an effective methodology to suppress gene function. The siRNA can be synthesized easily; however, a major obstacle in the use of siRNA as therapeutics is the difficulty involved in effective in vivo delivery.
To investigate the efficiency of nonviral ultrasound-microbubble-mediated in vivo siRNA delivery, we used a fluorescein-labeled siRNA, green fluorescent protein (GFP) siRNA, and intercellular adhesion molecule (ICAM)-1 siRNA in murine arteries. Murine femoral arteries were injured using flexible wires to establish arterial injury.
The fluorescein-labeled siRNA and GFP siRNA showed that this nonviral approach could deliver siRNA into target arteries effectively without any tissue damage and systemic adverse effects. ICAM-1 siRNA transfection into murine injured arteries significantly suppressed the development of neointimal formation in comparison to those in the control group. Immunohistochemistry revealed that accumulation of T cells and adhesion molecule positive cells was observed in nontreated injured arteries, whereas siRNA suppressed accumulation.
The nonviral ultrasound-microbubble delivery of siRNA ensures effective transfection into target arteries. ICAM-1 siRNA has the potential to suppress arterial neointimal formation. Transfection of siRNA can be beneficial for the clinical treatment of cardiovascular and other inflammatory diseases.
本研究旨在探讨小干扰核糖核酸（siRNA）在鼠动脉中的效率。我们使用非病毒超声-微泡介导的体内基因传递系统进行转染。
siRNA 是一种有效抑制基因功能的方法。siRNA 易于合成；然而，siRNA 作为治疗剂的一个主要障碍是有效体内传递的困难。
为了研究非病毒超声-微泡介导的体内 siRNA 传递效率，我们在鼠动脉中使用了荧光素标记的 siRNA、绿色荧光蛋白（GFP）siRNA 和细胞间黏附分子（ICAM）-1 siRNA。使用柔性丝在鼠股动脉中造成动脉损伤，以建立动脉损伤模型。
荧光素标记的 siRNA 和 GFP siRNA 表明，这种非病毒方法可以有效地将 siRNA 递送至靶动脉，而不会造成任何组织损伤和全身不良反应。与对照组相比，ICAM-1 siRNA 转染到鼠损伤动脉中显著抑制了新生内膜形成的发展。免疫组织化学显示，未经处理的损伤动脉中观察到 T 细胞和黏附分子阳性细胞的聚集，而 siRNA 抑制了聚集。
非病毒超声-微泡递送 siRNA 可确保将 siRNA 有效转染至靶动脉。ICAM-1 siRNA 具有抑制动脉新生内膜形成的潜力。siRNA 的转染可能有益于心血管和其他炎症性疾病的临床治疗。
