Title
A retro-inverso cell-penetrating peptide for siRNA delivery
Author
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
Year
2017
Journal
Journal of Nanobiotechnology
Abstract
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 specifc delivery system. Among them, cell-penetrating peptides (CPP) have been shown to transfer efciently 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. 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. 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).
Instrument
J-810
Keywords
Circular dichroism, Secondary structure, Stereochemistry, Nanostructures, RNA binding, Vesicle interactions, Thermal stability, Biochemistry