Reductively Dissociable siRNA-Polymer Hybrid Nanogels for Efficient Targeted Gene Silencing

Cheol Am Hong; Jee Seon Kim; Soo Hyeon Lee; Won Ho Kong; Tae Gwan Park; Hyejung Mok; Yoon Sung Nam

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Reductively Dissociable siRNA-Polymer Hybrid Nanogels for Efficient Targeted Gene Silencing

机译：可还原解离的siRNA-聚合物杂化纳米凝胶，可有效靶向基因沉默。

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A highly efficient approach for target-specific gene silencing based on a reductively dissociable nanogel incorporating small interfering RNA (siRNA) crosslinked with linear polyethylenimine (LPEI) via disulfide bonds is presented. Thiol-terminated siRNA at both 3'-ends is electrostatically complexed with thiol-grafted LPEI. The prepared siRNA/LPEI complex contains inter-and intramolecular linkages, generating a mutually crosslinked siRNA/LPEI nanogel (MCN) that exhibits excellent structural stability against the addition of heparin but is readily disintegrated to biologically active, monomeric siRNA upon exposure to reductive conditions. Accordingly, the highly condensed, stable MCN shows greatly enhanced cellular uptake and gene silencing efficiency compared to the siRNA/LPEI complexes without crosslinks or with only LPEI-mediated crosslinks.

机译：提出了一种高效的靶向特异性基因沉默方法，该方法基于可还原解离的纳米凝胶，该凝胶包含通过二硫键与线性聚乙烯亚胺（LPEI）交联的小干扰RNA（siRNA）。在两个3'端均以巯基封端的siRNA与巯基接枝的LPEI进行静电复合。制备的siRNA / LPEI复合物包含分子间和分子内连接，生成相互交联的siRNA / LPEI纳米凝胶（MCN），相对于添加肝素显示出极好的结构稳定性，但在暴露于还原条件下易于分解为具有生物学活性的单体siRNA。因此，与没有交联或仅具有LPEI介导的交联的siRNA / LPEI复合物相比，高度浓缩，稳定的MCN显示出大大增强的细胞摄取和基因沉默效率。

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《Advanced Functional Materials》 |2013年第3期|316-322|共7页
作者
Cheol Am Hong; Jee Seon Kim; Soo Hyeon Lee; Won Ho Kong; Tae Gwan Park; Hyejung Mok; Yoon Sung Nam;
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Department of Biological Sciences Korea Advanced Institute of Science and Technology 291 Daehak-ro, Yuseung-gu, Daejeon 305-701, Republic of Korea;

Department of Biological Sciences Korea Advanced Institute of Science and Technology 291 Daehak-ro, Yuseung-gu, Daejeon 305-701, Republic of Korea;

Department of Biological Sciences Korea Advanced Institute of Science and Technology 291 Daehak-ro, Yuseung-gu, Daejeon 305-701, Republic of Korea;

Department of Biological Sciences Korea Advanced Institute of Science and Technology 291 Daehak-ro, Yuseung-gu, Daejeon 305-701, Republic of Korea;

Department of Biological Sciences Korea Advanced Institute of Science and Technology 291 Daehak-ro, Yuseung-gu, Daejeon 305-701, Republic of Korea;

Department of Bioscience and Biotechnology Konkuk University Seoul 143-701, Republic of Korea;

Department of Biological Sciences Korea Advanced Institute of Science and Technology 291 Daehak-ro, Yuseung-gu, Daejeon 305-701, Republic of Korea,Department of Materials Science and Engineering KAIST Institute for NanoCentury (KINC) and BioCentury (KIB) Korea Advanced Institute of Science and Technology 291 Daehak-ro, Yuseung-gu, Daejeon 305-701, Republic of Korea;

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Reductively Dissociable siRNA-Polymer Hybrid Nanogels for Efficient Targeted Gene Silencing

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