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

Klein, P. M., Reinhard, S., Lee, D.-J., Müller, K., Ponader, D., Hartmann, L., et al. (2016). Precise redox-sensitive cleavage sites for improved bioactivity of siRNA lipopolyplexes. Nanoscale, 8(42), 18098-18104. doi:10.1039/C6NR05767E.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-BB26-3 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002B-BB27-1
Genre: Journal Article

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 Creators:
Klein, Philipp Michael, Author
Reinhard, Sören, Author
Lee, Dian-Jang, Author
Müller, Katharina, Author
Ponader, Daniela1, Author              
Hartmann, Laura, Author
Wagner, Ernst, Author
Affiliations:
1Laura Hartmann, Biomolekulare Systeme, Max Planck Institute of Colloids and Interfaces, Max Planck Society, ou_1863305              

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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.

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 Dates: 2016-10-072016
 Publication Status: Published in print
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 Identifiers: DOI: 10.1039/C6NR05767E
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Title: Nanoscale
Source Genre: Journal
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Publ. Info: Cambridge, UK : Royal Society of Chemistry
Pages: - Volume / Issue: 8 (42) Sequence Number: - Start / End Page: 18098 - 18104 Identifier: ISSN: 2040-3364