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The reduced‐charge melittin analogue MelP5 improves the transfection of non‐viral DNA nanoparticles
Journal article   Open access   Peer reviewed

The reduced‐charge melittin analogue MelP5 improves the transfection of non‐viral DNA nanoparticles

Nathan A. Delvaux and Kevin G. Rice
Journal of peptide science, Vol.28(8), pp.e3404-n/a
08/2022
DOI: 10.1002/psc.3404
PMCID: PMC10069327
PMID: 35001445
url
https://pmc.ncbi.nlm.nih.gov/articles/PMC10069327/pdf/nihms-1864626.pdfView
Open Access

Abstract

Melittin is a 26-amino acid amphiphilic alpha-helical peptide derived from honeybee venom. Prior studies have incorporated melittin into non-viral delivery systems to effect endosomal escape of DNA nanoparticles and improve transfection efficiency. Recent advances have led to the development of two newer melittin analogues, MelP5 and Macrolittin 70, with improved pore formation in lipid bilayers while possessing fewer positive charges relative to natural melittin. Consequently, MelP5 and Macrolittin 70 were conjugated through a disulfide bond to a DNA binding polyacridine peptide. The resulting peptide conjugates were used to prepare DNA nanoparticles to compare their relative endosomolytic potency by transfection of HepG2 cells. Melittin and MelP5 conjugates were equally potent at mediating in vitro gene transfer, whereas PEGylation of DNA nanoparticles revealed improved transfection with MelP5 relative to melittin. The results demonstrate the ability to substitute a potent, reduced-charge analogue of melittin to improve overall DNA nanoparticle biocompatibility needed for in vivo testing.

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