Journal of Nanobiotechnology (Apr 2017)

A retro-inverso cell-penetrating peptide for siRNA delivery

  • Anaïs Vaissière,
  • Gudrun Aldrian,
  • Karidia Konate,
  • Mattias F. Lindberg,
  • Carole Jourdan,
  • Anthony Telmar,
  • Quentin Seisel,
  • Frédéric Fernandez,
  • Véronique Viguier,
  • Coralie Genevois,
  • Franck Couillaud,
  • Prisca Boisguerin,
  • Sébastien Deshayes

DOI
https://doi.org/10.1186/s12951-017-0269-2
Journal volume & issue
Vol. 15, no. 1
pp. 1 – 18

Abstract

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Abstract Background Small interfering RNAs (siRNAs) are powerful tools to control gene expression. However, due to their poor cellular permeability and stability, their therapeutic development requires a specific delivery system. Among them, cell-penetrating peptides (CPP) have been shown to transfer efficiently siRNA inside the cells. Recently we developed amphipathic peptides able to self-assemble with siRNAs as peptide-based nanoparticles and to transfect them into cells. However, despite the great potential of these drug delivery systems, most of them display a low resistance to proteases. Results Here, we report the development and characterization of a new CPP named RICK corresponding to the retro-inverso form of the CADY-K peptide. We show that RICK conserves the main biophysical features of its L-parental homologue and keeps the ability to associate with siRNA in stable peptide-based nanoparticles. Moreover the RICK:siRNA self-assembly prevents siRNA degradation and induces inhibition of gene expression. Conclusions This new approach consists in a promising strategy for future in vivo application, especially for targeted anticancer treatment (e.g. knock-down of cell cycle proteins). Graphical abstract RICK-based nanoparticles: RICK peptides and siRNA self-assemble in peptide-based nanoparticles to penetrate into the cells and to induce target protein knock-down.

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