A retro-inverso cell-penetrating peptide for siRNA delivery

• Main Authors: 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
• Format: Article
• Language: English
• Published: BMC 2017-04-01
• Series: Journal of Nanobiotechnology
• Subjects: Enantiomer; d-Amino acids; Retro-inverso; siRNA delivery; Cell penetrating peptides; Nanoparticle
• Online Access: http://link.springer.com/article/10.1186/s12951-017-0269-2

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.