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Article Dans Une Revue Journal of Nanobiotechnology Année : 2021

WRAP-based nanoparticles for siRNA delivery: a SAR study and a comparison with lipid-based transfection reagents

Résumé

Abstract Recently, we designed novel amphipathic cell-penetrating peptides, called WRAP, able to transfer efficiently siRNA molecules into cells. In order to gain more information about the relationship between amino acid composition, nanoparticle formation and cellular internalization of these peptides composed of only three amino acids (leucine, arginine and tryptophan), we performed a structure–activity relationship (SAR) study. First, we compared our WRAP1 and WRAP5 peptides with the C6M1 peptide also composed of the same three amino acids and showing similar behaviors in siRNA transfection. Afterwards, to further define the main determinants in the WRAP activity, we synthesized 13 new WRAP analogues harboring different modifications like the number and location of leucine and arginine residues, the relative location of tryptophan residues, as well as the role of the α-helix formation upon proline insertions within the native WRAP sequence. After having compared the ability of these peptides to form peptide-based nanoparticles (PBNs) using different biophysical methods and to induce a targeted gene silencing in cells, we established the main sequential requirements of the amino acid composition of the WRAP peptide. In addition, upon measuring the WRAP-based siRNA transfection ability into cells compared to several non-peptide transfection agents available on the markets, we confirmed that WRAP peptides induced an equivalent level of targeted gene silencing but in most of the cases with lower cell toxicity as clearly shown in clonogenic assays.
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Dates et versions

hal-03326822 , version 1 (29-08-2021)

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Karidia Konate, Emilie Josse, Milana Tasic, Karima Redjatti, Gudrun Aldrian, et al.. WRAP-based nanoparticles for siRNA delivery: a SAR study and a comparison with lipid-based transfection reagents. Journal of Nanobiotechnology, 2021, 19 (1), ⟨10.1186/s12951-021-00972-8⟩. ⟨hal-03326822⟩
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