Design of pH‐sensitive peptides from natural antimicrobial peptides for enhancing polyethylenimine‐mediated gene transfection

Zhang, Shikun; Song, Jin‐Wen; Li, Su-Bo; Gao, Hongwei; Chang, Hong-Yu; Jia, Lili; Gao, Feng; Yang, Tan; Ji, Shou‐Ping

doi:10.1002/jgm.2955

Cited by 7 publications

(6 citation statements)

References 49 publications

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“…Glu is partially protonated at pH 5.0, which appears to be sufficient for inducing the pH responsiveness of these peptides 17,18,34 . Replacement of the positively‐charged residues of the naturally occurring membrane‐permeabilizing antimicrobial peptide with Glu yielded the pH‐sensitive endosomolytic peptides, which could enhance the PEI‐mediated transfection efficiency 11 …”

Section: Discussionmentioning

confidence: 99%

“…The incorporation of pH-sensitive peptides into polyplexes enhanced the PEI-mediated transfection efficiency, corresponding to up to 42-fold higher luciferase activity compared to that of PEI alone. 11 The results indicate that replacement of positively-charged residues with glutamic acid residues in the AMP sequence yields pH-sensitive peptides, which enhance the transfection efficiency of PEI/DNA polyplexes.…”

Section: Introductionmentioning

confidence: 92%

“…17,18,34 Replacement of the positively-charged residues of the naturally occurring membrane-permeabilizing antimicrobial peptide with Glu yielded the pH-sensitive endosomolytic peptides, which could enhance the PEI-mediated transfection efficiency. 11 The present study aimed to investigate the effect of the number of glutamic acids substituted for positively-charged residues on the endosomal escape activity of AR-23 and the ability of modified AR-23…”

Section: Intracellular Trafficking Of the Polyplexesmentioning

confidence: 99%

“…[7][8][9] The addition of pH-sensitive peptides has been shown to potentially enhance gene expression of non-viral gene delivery vectors. 10,11 Melittin, a 26-residue peptide from the venom of Apis mellifera honeybees, is a well-studied endosomal disrupting peptide. 12,13 Melittin or its analogues have been incorporated into polyplex formulations to increase transfection efficiency in different cell lines.…”

Section: Introductionmentioning

confidence: 99%

“…Strategies to achieve endosomolysis have traditionally been based on osmotic agents, fusogenic lipids and fusogenic peptides 7–9 . The addition of pH‐sensitive peptides has been shown to potentially enhance gene expression of non‐viral gene delivery vectors 10,11 …”

Section: Introductionmentioning

confidence: 99%

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Antimicrobial peptide AR‐23 derivatives with high endosomal disrupting ability enhance poly(l‐lysine)‐mediated gene transfer

Zhang¹,

Gong

Zhang³

et al. 2020

The Journal of Gene Medicine

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Background: pH-sensitive peptides are a relatively new strategy for conquering the poor endosomal release of cationic polymer-mediated transfection. Modification of antimicrobial peptides by exchanging positively-charged residues with negativelycharged glutamic acid residues (Glu) greatly improves its lytic activity at the endosomal pH, which could improve cationic polymer-mediated transfection. Methods: In the present study, we investigated the effect of the number of Glu substituted for positively-charged residues on the endosomal escape activity of AR-23 and the ability of mutated AR-23 with respect to enhancing cationic polymermediated transfection. Three analogs were synthesized by replacing the positivelycharged residues in the AR-23 sequence with Glu one-by-one. Results: The pH-sensitive lysis ability of the peptides, the effect of peptides on the physicochemical characteristics, the intracellular trafficking, the transfection efficiency and the cytotoxicity of the polyplexes were determined. Increased lytic activity of peptides was observed with the increased number of Glu replacement in the AR-23 sequence at acidic pH. The number of Glu substituted for positively-charged residues of AR-23 dramatically affects its lysis ability at neutral pH. Triple-Glu substitution in the AR-23 sequence greatly improved poly(L-lysine)-mediated gene transfection efficiency at the same time as maintaining low cytotoxicity. Conclusions: The results indicate that replacement of positively-charged residues with sufficient Glu residues may be considered as a method for designing pHsensitive peptides, which could be applied as potential enhancers for improving cationic polymer-mediated transfection.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%