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Evaluating the efficient and safe transfer of nucleic acids into cells with a Cell-Penetrating Peptide: A SAR study
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International audience. Recently, we designed novel amphipathic cell-penetrating peptides, called WRAP, able to transfer efficiently siRNA molecules into cells [1]. 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 residues), we performed a structure-activity relationship (SAR) study based on the synthesis of 13 new WRAP analogs harboring different modifications, deletions, substitutions… We compared the ability of these peptides to form peptide-based nanoparticles (PBNs) with siRNAs and to induce a specific gene silencing in cells using different biophysical methods [2]. We established the main sequential requirements for the amino acid composition of this WRAP peptide. In addition, we compared the WRAP peptide to several cationic lipid-based transfection agents and confirmed that WRAP peptides induced an equivalent level of specific gene silencing, but in most of the cases, with lower cell toxicity.References.[1] Konate, K., Dussot, M., Aldrian, G., Vaissière, A., Viguier, I, Ferreiro, Neira I., Couillaud, F., Vivès, E., Boisguerin, P., Deshayes, S. «Peptide-based nanoparticles to rapidly and efficiently “Wrap’n Roll" siRNA into cells ». 2019, Bioconjugate Chemistry, vol 30, Issue 3, 592-603. DOI: 10.1021/acs.bioconjchem.8b00776[2] Konate, K., Josse, E., Tasic, M., Redjati, K., Aldrian, G., Deshayes, S., Boisguerin, P. and Vivès, E. “ WRAP-based nanoparticles for siRNA delivery: a SAR study and a comparison with lipid-based transfection reagents”. J Nanobiotechnol 19, 236 (2021). DOI: 10.1186/s12951-021-00972-8
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