Issue 38, 2023

Magainin 2-derived stapled peptides derived with the ability to deliver pDNA, mRNA, and siRNA into cells

Abstract

We have developed cell-penetrating stapled peptides based on the amphipathic antimicrobial peptide magainin 2 for intracellular delivery of nucleic acids such as pDNA, mRNA, and siRNA. Various types of stapled peptides with a cross-linked structure were synthesised in the hydrophobic region of the amphipathic structure, and their efficacy in intracellular delivery of pDNA was evaluated. The results showed that the stapled peptide st7-5 could deliver pDNA into cells. To improve the deliverability of st7-5, we further designed st7-5_R, in which the Lys residues were replaced by Arg residues. The peptide st7-5_R formed compact and stable complexes with pDNA and was able to efficiently transfer pDNA into the cell. In addition to pDNA, st7-5_R was also able to deliver mRNA and siRNA into the cell. Thus, st7-5_R is a novel peptide that can achieve efficient intracellular delivery of three different nucleic acids.

Graphical abstract: Magainin 2-derived stapled peptides derived with the ability to deliver pDNA, mRNA, and siRNA into cells

Supplementary files

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Article information

Article type
Edge Article
Submitted
08 ago. 2023
Accepted
27 ago. 2023
First published
14 sep. 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 10403-10410

Magainin 2-derived stapled peptides derived with the ability to deliver pDNA, mRNA, and siRNA into cells

M. Hirano, H. Yokoo, C. Goto, M. Oba, T. Misawa and Y. Demizu, Chem. Sci., 2023, 14, 10403 DOI: 10.1039/D3SC04124G

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