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

Authors

  • Cheol Am Hong,

    1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseung-gu, Daejeon 305-701, Republic of Korea
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  • Jee Seon Kim,

    1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseung-gu, Daejeon 305-701, Republic of Korea
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  • Soo Hyeon Lee,

    1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseung-gu, Daejeon 305-701, Republic of Korea
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  • Won Ho Kong,

    1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseung-gu, Daejeon 305-701, Republic of Korea
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  • Tae Gwan Park,

    1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseung-gu, Daejeon 305-701, Republic of Korea
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  • Hyejung Mok,

    Corresponding author
    1. Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea
    • Department of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, Republic of Korea.
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  • Yoon Sung Nam

    Corresponding author
    1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseung-gu, Daejeon 305-701, Republic of Korea
    2. 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
    • Department of Biological Sciences, Korea Advanced Institute of Science and Technology, 291 Daehak-ro, Yuseung-gu, Daejeon 305-701, Republic of Korea
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Abstract

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.

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