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Issue 42, 2016
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Precise redox-sensitive cleavage sites for improved bioactivity of siRNA lipopolyplexes

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Abstract

Lipo-oligomers have been proven as potent siRNA carriers based on stable electrostatic and hydrophobic complex formation and endosomal membrane destabilization. Although high stability of siRNA polyplexes is desirable in the extracellular space and cellular uptake, intracellular disassembly is important for the cytosolic release of siRNA and RNA-induced silencing complex formation. To improve the release, bioreducible sequence-defined lipo-oligomers were synthesized by solid-phase assisted synthesis using the disulfide building block Fmoc-succinoyl-cystamine for precise positioning of a disulfide unit between a lipophilic diacyl (bis-myristyl, bis-stearyl or bis-cholestanyl) domain and an ionizable oligocationic siRNA binding unit. Reducible siRNA polyplexes show higher gene silencing efficacy and lower cytotoxicity than their stable analogs, consistent with glutathione-triggered siRNA release and reduced lytic activity.

Graphical abstract: Precise redox-sensitive cleavage sites for improved bioactivity of siRNA lipopolyplexes

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Publication details

The article was received on 21 Jul 2016, accepted on 06 Oct 2016 and first published on 07 Oct 2016


Article type: Paper
DOI: 10.1039/C6NR05767E
Citation: Nanoscale, 2016,8, 18098-18104
  • Open access: Creative Commons BY-NC license
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    Precise redox-sensitive cleavage sites for improved bioactivity of siRNA lipopolyplexes

    P. M. Klein, S. Reinhard, D. Lee, K. Müller, D. Ponader, L. Hartmann and E. Wagner, Nanoscale, 2016, 8, 18098
    DOI: 10.1039/C6NR05767E

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