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Issue 3, 2016
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Delivery of siRNA using ternary complexes containing branched cationic peptides: the role of peptide sequence, branching and targeting

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Abstract

Ternary nanocomplexes, composed of bifunctional cationic peptides, lipids and siRNA, as delivery vehicles for siRNA have been investigated. The study is the first to determine the optimal sequence and architecture of the bifunctional cationic peptide used for siRNA packaging and delivery using lipopolyplexes. Specifically three series of cationic peptides of differing sequence, degrees of branching and cell-targeting sequences were co-formulated with siRNA and vesicles prepared from a 1 : 1 molar ratio of the cationic lipid DOTMA and the helper lipid, DOPE. The level of siRNA knockdown achieved in the human alveolar cell line, A549-luc cells, in both reduced serum and in serum supplemented media was evaluated, and the results correlated to the nanocomplex structure (established using a range of physico-chemical tools, namely small angle neutron scattering, transmission electron microscopy, dynamic light scattering and zeta potential measurement); the conformational properties of each component (circular dichroism); the degree of protection of the siRNA in the lipopolyplex (using gel shift assays) and to the cellular uptake, localisation and toxicity of the nanocomplexes (confocal microscopy). Although the size, charge, structure and stability of the various lipopolyplexes were broadly similar, it was clear that lipopolyplexes formulated from branched peptides containing His-Lys sequences perform best as siRNA delivery agents in serum, with protection of the siRNA in serum balanced against efficient release of the siRNA into the cytoplasm of the cell.

Graphical abstract: Delivery of siRNA using ternary complexes containing branched cationic peptides: the role of peptide sequence, branching and targeting

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Publication details

The article was received on 05 Nov 2015, accepted on 11 Jan 2016 and first published on 22 Jan 2016


Article type: Paper
DOI: 10.1039/C5MB00754B
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Mol. BioSyst., 2016,12, 934-951
  • Open access: Creative Commons BY license
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    Delivery of siRNA using ternary complexes containing branched cationic peptides: the role of peptide sequence, branching and targeting

    L. Kudsiova, K. Welser, F. Campbell, A. Mohammadi, N. Dawson, L. Cui, H. C. Hailes, M. J. Lawrence and A. B. Tabor, Mol. BioSyst., 2016, 12, 934
    DOI: 10.1039/C5MB00754B

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