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

  1. Cheol Am Hong1,
  2. Jee Seon Kim1,
  3. Soo Hyeon Lee1,
  4. Won Ho Kong1,
  5. Tae Gwan Park1,
  6. Hyejung Mok2,*,
  7. Yoon Sung Nam1,3,*

Article first published online: 24 AUG 2012

DOI: 10.1002/adfm.201200780

Issue

Advanced Functional Materials

Advanced Functional Materials

Volume 23, Issue 3, pages 316–322, January 21, 2013

Additional Information

How to Cite

Hong, C. A., Kim, J. S., Lee, S. H., Kong, W. H., Park, T. G., Mok, H. and Nam, Y. S. (2013), Reductively Dissociable siRNA-Polymer Hybrid Nanogels for Efficient Targeted Gene Silencing. Adv. Funct. Mater., 23: 316–322. doi: 10.1002/adfm.201200780

Author Information

  1. 1

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

  2. 2

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

  3. 3

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

Publication History

  1. Issue published online: 11 JAN 2013
  2. Article first published online: 24 AUG 2012
  3. Manuscript Revised: 3 JUN 2012
  4. Manuscript Received: 2 MAR 2012

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Keywords:

  • small interfering RNA (siRNA);
  • nanogels;
  • reducible crosslinking;
  • gene delivery;
  • gene silencing

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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