Systemic and specific delivery of small interfering RNAs to the liver mediated by apolipoprotein A-I
Systemic and specific delivery of small interfering RNAs to the liver mediated by apolipoprotein A-I
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DOI：
10.1038/sj.mt.6300168
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发表时间：
2007-06-01
影响因子：
12.4
通讯作者：
Kim, Meehyein
中科院分区：
文献类型：
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作者：
Kim, Soo In;Shin, Duckhyang;Kim, Meehyein
小干扰RNA（siRNA）的组织靶向递送必须在RNA干扰（RNAi）技术可用于实际治疗方法之前实现。在这项研究中，载脂蛋白A-I（载脂蛋白A-I）的潜力，用于核酸的全身输送到肝脏是使用实时体内成像。作为概念验证，将针对肝炎B病毒（HBV）的合成siRNA配制成载脂蛋白A-I和1，2-二油酰基-3-三甲基铵-丙烷（DOTAP）/胆固醇（DTC-Apo）的复合物，并静脉内（IV）注射到携带复制型HBV的小鼠模型中。我们表明，这些纳米颗粒的管理可以显着减少受体介导的内吞作用的病毒蛋白质表达。载脂蛋白A-I介导的siRNA递送方法的优点是其肝脏特异性、低剂量下的有效性（
Tissue-targeted delivery of small interfering RNA (siRNA) must be achieved before RNA interference (RNAi) technology can be used in practical therapeutic approaches. In this study, the potential of apolipoprotein A-I (apo A-I) for the systemic delivery of nucleic acids to the liver is demonstrated using real-time in vivo imaging. As a proof of concept, synthetic siRNAs against hepatitis B virus (HBV) were formulated into complexes of apo A-I and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol (DTC-Apo) and injected intravenously (IV) into a mouse model carrying replicating HBV. We show that administration of these nanoparticles can significantly reduce viral protein expression by receptor-mediated endocytosis. The advantages of the apo A-I-mediated siRNA delivery method are its liver specificity, its effectiveness at low doses (