通过各种递送方法将小干扰RNA（siRNA）导入靶组织的有效性。
Effectiveness of siRNA uptake in target tissues by various delivery methods.
作者信息
Larson Shawn D, Jackson Lindsey N, Chen L Andy, Rychahou Piotr G, Evers B Mark
机构信息
Department of Surgery, The University of Texas Medical Branch, Galveston, Tex, USA.
出版信息
Surgery. 2007 Aug;142(2):262-9. doi: 10.1016/j.surg.2007.03.011.
BACKGROUND
RNA interference offers clinical potential as a therapeutic modality for a variety of diseases; the efficacy of in vivo delivery remains poorly understood. The purpose of our study was to compare and contrast short interfering RNA (siRNA) uptake in vivo using various delivery techniques.
METHODS
DY547- and rhodamine-labeled siRNA was administered to mice by one of four delivery methods: (1) hydrodynamic intravenous tail vein injection, (2) standard intravenous tail vein injection, (3) intraperitoneal injection, and (4) rectal administration. Mice were killed over a time course; representative tissue samples were collected and analyzed using fluorescent microscopy to determine siRNA uptake.
RESULTS
siRNA uptake was noted in the liver, kidney, pancreas, spleen, and bone marrow by both hydrodynamic and standard IV injection. siRNA uptake was detected in the spleen, liver, and bone marrow after intraperitoneal administration. Rectal administration resulted in siRNA uptake in the spleen, bone marrow, and colon.
CONCLUSION
Our results demonstrate differential siRNA uptake depending on delivery technique. Importantly, our results demonstrate the potential of siRNA as a systemic therapeutic option in vivo for selected disease processes.
背景
RNA干扰作为多种疾病的一种治疗方式具有临床应用潜力；但其体内递送的效果仍了解不足。我们研究的目的是比较和对比使用各种递送技术在体内摄取小干扰RNA（siRNA）的情况。
方法
通过以下四种递送方法之一将Dy547和罗丹明标记的siRNA给予小鼠：（1）水动力静脉尾静脉注射，（2）标准静脉尾静脉注射，（3）腹腔注射，以及（4）直肠给药。在一段时间内处死小鼠；收集代表性组织样本并使用荧光显微镜进行分析以确定siRNA的摄取情况。
结果
通过水动力和标准静脉注射在肝脏、肾脏、胰腺、脾脏和骨髓中均观察到siRNA的摄取。腹腔给药后在脾脏、肝脏和骨髓中检测到siRNA的摄取。直肠给药导致在脾脏、骨髓和结肠中摄取siRNA。
结论
我们的结果表明根据递送技术不同siRNA的摄取情况存在差异。重要的是，我们的结果证明了siRNA作为体内特定疾病进程的全身治疗选择的潜力。
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