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

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 comp...

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Bibliographic Details
Published in:	Journal of nanobiotechnology Vol. 19; no. 1; p. 236
Main Authors:	Konate, Karidia, Josse, Emilie, Tasic, Milana, Redjatti, Karima, Aldrian, Gudrun, Deshayes, Sébastien, Boisguérin, Prisca, Vivès, Eric
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 11-08-2021 BioMed Central BMC
Subjects:	Amino acid composition Amino Acid Sequence Amino acids Analysis Cell Line, Tumor Cell-Penetrating Peptides Chemical properties Composition Compression Bandages Drug Delivery Systems Drugs Gene silencing Gene Silencing - drug effects Glioblastoma Health aspects Humans Indicators and Reagents - chemistry Internalization Investigations Leucine Life Sciences Lipids Lipids - chemistry Methods Nanoparticle Nanoparticles Nanoparticles - chemistry Peptides Plasmids Proline Reagents Residues RNA, Small Interfering - chemistry RNA, Small Interfering - pharmacology siRNA siRNA delivery Structure-Activity Relationship Structure-activity relationship (Pharmacology) Structure-activity relationships Toxicity Transfection Tryptophan France siRNA delivery Cell-penetrating peptides Nanoparticle Structure–activity relationship
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1477-3155 1477-3155
DOI:	10.1186/s12951-021-00972-8