PepFect14 Signaling and Transfection

Falato, Luca; Gestin, Maxime; Langel, Ülo

doi:10.1007/978-1-0716-1752-6_15

Cited by 3 publications

(3 citation statements)

References 66 publications

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“…The recent definition of CPPs (Langel 2022), previously also known as protein/peptide transduction domains, PTD, Trojan peptides or shuttling peptides, summarizes the diffuse diversity of a huge class of peptides with multiple bioactive properties and drug delivery abilities:…”

Section: Cell-penetrating Peptidesmentioning

confidence: 99%

“…Calcium signal activity was tested following the application of a hemichannel block ing peptide, Gap19 (nine aa from connexin 43 cytoplas mic loop), complexed with PF6, showing the reduction of astrocyte response amplitudes and the proportion of SE astrocytes to the EtOH treatment in enriched astrocyte cultures (Kim et al 2021). Nanoparticles of PF14, complexed with Heat Shock Protein (HSP70), suggested first by docking (Dowaidar et al 2017c), showed delivery into Bomirsky Hamster Melanoma cells (Falato et al 2022).…”

Section: Nucleic Acid Delivery By Complexation Pepfects and Nickfectsmentioning

confidence: 99%

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Nucleic acid delivery by cell-penetrating peptides

Langel

2023

PEAS

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Section: Cell-penetrating Peptidesmentioning

confidence: 99%

Section: Nucleic Acid Delivery By Complexation Pepfects and Nickfectsmentioning

confidence: 99%

Nucleic acid delivery by cell-penetrating peptides

Langel

2023

PEAS

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“…Polyornithines outperform polylysines in transfection efficiency, which was attributed to a tighter association with the ON . Moreover, in PF14, all isoleucines present in PF3 were replaced with leucines to reduce steric repulsion between the cargo (ON) and peptide . At higher concentrations, however, PF14 is also cytotoxic through its membrane-active nature, which results from its amphipathic character.…”

Section: Introductionmentioning

confidence: 99%

Deciphering Structural Determinants Distinguishing Active from Inactive Cell-Penetrating Peptides for Cytosolic mRNA Delivery

Egberink,

van Asbeck,

Boswinkel

et al. 2023

Bioconjugate Chem.

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The formation of noncovalent complexes by mixing of positively charged polymers with negatively charged oligonucleotides (ONs) is a widely explored concept in nanomedicine to achieve cellular delivery of ONs. Uptake of ON complexes occurs through endocytosis, which then requires release of ON from endosomes. As one type of polymer, cell-penetrating peptides (CPPs) are being used which are peptides of about 8−30 amino acids in length. However, only a few CPPs yield effective cytosolic ON delivery and activity. Several strategies have been devised to increase cellular uptake and enhance endosomal release, among which an increase of osmotic pressure through the so-called proton sponge effect, disruption of membrane integrity through membrane activity, and disulfidemediated polymerization. Here, we address the relevance of these concepts for mRNA delivery by incorporating structural features into the human lactoferrin-derived CPP, which shows uptake but not delivery. The incorporation of histidines was explored to address osmotic pressure and structural motifs of the delivery-active CPP PepFect14 (PF14) to address membrane disturbance, and finally, the impact of polymerization was explored. Whereas oligomerization increased the stability of polyplexes against heparin-induced decomplexation, neither this approach nor the incorporation of histidine residues to promote a proton-sponge effect yielded activity. Also, the replacement of arginine residues with lysine or ornithine residues, as in PF14, was without effect, even though all polyplexes showed cellular uptake. Ultimately, sufficient activity could only be achieved by transferring amphipathic sequence motifs from PF14 into the hLF context with some benefit of oligomerization demonstrating overarching principles of delivery for CPPs, lipid nanoparticles, and other types of delivery polymers.

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Cell-Translocation Mechanisms of CPPs

Langel

2023

CPP, Cell-Penetrating Peptides

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PepFect14 Signaling and Transfection

Cited by 3 publications

References 66 publications

Nucleic acid delivery by cell-penetrating peptides

Nucleic acid delivery by cell-penetrating peptides

Deciphering Structural Determinants Distinguishing Active from Inactive Cell-Penetrating Peptides for Cytosolic mRNA Delivery

Cell-Translocation Mechanisms of CPPs

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