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Aptamer-incorporated DNA Holliday junction for the targeted delivery of siRNA

机译：适用于靶向递送siRNA的DNA Holliday结合

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There have been unmet needs of developing carrier-free siRNA delivery systems to overcome the undesirable cellular toxicity and immunogenicity of conventional delivery systems such as cationic lipids and polymers. Various nucleic acid nanostructures have been proposed to achieve this goal, however many of them required potent ligands for the intracellular delivery of siRNA. Among various ligands, aptamers received much interest due to their facile preparation process as well as a high binding affinity toward target receptors. In addition, nucleic acid based aptamers can be easily incorporated with various nucleic acid nanostructures through a simple base-pair hybridization. In this study, aptamer incorporated siRNA (Apt-siRNA) was self-assembled with DNA Holliday junction for enhancing targeted delivery of siRNA to the Mucin 1 (MUC1) overexpressing cancer cells. Molecularly self-assembled Holliday DNA junction with Apt-siRNA was analyzed to confirm their cellular uptake and gene silencing as compared to the Apt-siRNA alone in the GFP expressing KB cells. The multivalent Apt-siRNA DNA nanostructure (Holliday-Apt-siRNA) clearly showed their superior potency over the Apt-siRNA alone suggesting their use in carrier-free siRNA delivery systems. (C) 2017 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.
机译：为了克服阳离子脂质和聚合物等传统递送系统的不良细胞毒性和免疫原性，开发无载体siRNA递送系统的需求尚未得到满足。为了实现这一目标，人们提出了各种核酸纳米结构，然而其中许多都需要强有力的配体来在细胞内传递siRNA。在各种配体中，适体因其制备过程简单，对靶受体具有较高的结合亲和力而备受关注。此外，通过简单的碱基对杂交，基于核酸的适体可以很容易地与各种核酸纳米结构结合。在这项研究中，适体结合的siRNA（Apt-siRNA）与DNA Holliday连接点自组装，以增强siRNA对过度表达粘蛋白1（MUC1）的癌细胞的靶向递送。与表达GFP的KB细胞中单独使用Apt-siRNA相比，分析了具有Apt-siRNA的分子自组装Holliday DNA连接，以确认其细胞摄取和基因沉默。多价Apt-siRNA DNA纳米结构（Holliday Apt-siRNA）清楚地显示了其优于Apt-siRNA的效力，表明其可用于无载体siRNA递送系统。（C） 2017年，韩国工业与工程化学学会。由爱思唯尔B.V.出版。版权所有。

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