While siRNA is a potent therapeutic tool that can silence disease-causing mRNA, its in vivo potency can be compromised due to the lack of target tissue specificity. Here, we report a wireframe tetrahedral DNA nanostructure having a 20-mer duplex on each side that can be specifically distributed into the liver upon systemic administration. This liver-targeted DNA tetrahedron is employed as the carrier for liver-specific delivery of siRNA targeting ApoB1 mRNA, which is overexpressed in hypercholesterolemia. When delivered by a DNA tetrahedron, the siRNA can preferentially be accumulated in the liver and down-regulate the ApoB1 protein. As a result, the blood cholesterol level is also decreased by the siRNA. These results successfully demonstrate that the DNA tetrahedron is a promising carrier for liver-targeted delivery of therapeutic nucleic acids.

中文翻译：

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自组装的DNA四面体作为载体，用于在体内肝脏特异性递送siRNA。

尽管siRNA是一种有效的治疗工具，可以使引起疾病的mRNA沉默，但由于缺乏靶组织特异性，其体内功效可能会受到损害。在这里，我们报告的线框四面体DNA纳米结构在每侧具有20-mer双链体，可在全身给药后特异性地分布到肝脏中。这种以肝脏为靶标的DNA四面体被用作载体，用于肝脏特异性递送靶向ApoB1 mRNA的siRNA，后者在高胆固醇血症中过表达。当通过DNA四面体递送时，siRNA可以优先在肝脏中积累并下调ApoB1蛋白。结果，通过siRNA也降低了血液胆固醇水平。这些结果成功地证明了DNA四面体是用于肝脏靶向递送治疗性核酸的有希望的载体。