Designer Amyloid Cell-Penetrating Peptides for Potential Use as Gene Transfer Vehicles

• Published in: Biomolecules (Basel, Switzerland) Vol. 10; no. 1; p. 7
• Main Authors: Kokotidou, Chrysoula, Jonnalagadda, Sai Vamshi R, Orr, Asuka A, Vrentzos, George, Kretsovali, Androniki, Tamamis, Phanourios, Mitraki, And Anna
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 18-12-2019; MDPI
• Subjects: Amino acids; Amyloid - chemistry; Amyloid - metabolism; Amyloid - pharmacology; Antimicrobial activity; Biomaterials; Cell-Penetrating Peptides - chemistry; Cell-Penetrating Peptides - metabolism; Cell-Penetrating Peptides - pharmacology; Cytotoxicity; Deoxyribonucleic acid; Design; DNA; Enhancers; Escherichia coli - drug effects; Escherichia coli - genetics; Fibrils; Gene expression; Gene transfer; Gene Transfer Techniques; Internalization; Mammalian cells; Peptides; Plasmids; Plasmids - genetics; Plasmids - metabolism; Protein Conformation, beta-Strand; Proteins; Simulation; computational biology; peptide; amyloid; gene transfer; molecular dynamics; scaffold
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom10010007

Cell-penetrating peptides are used extensively to deliver molecules into cells due to their unique characteristics such as rapid internalization, charge, and non-cytotoxicity. Amyloid fibril biomaterials were reported as gene transfer or retroviral infection enhancers; no cell internalization of the peptides themselves is reported so far. In this study, we focus on two rationally and computationally designed peptides comprised of β-sheet cores derived from naturally occurring protein sequences and designed positively charged and aromatic residues exposed at key residue positions. The β-sheet cores bestow the designed peptides with the ability to self-assemble into amyloid fibrils. The introduction of positively charged and aromatic residues additionally promotes DNA condensation and cell internalization by the self-assembled material formed by the designed peptides. Our results demonstrate that these designer peptide fibrils can efficiently enter mammalian cells while carrying packaged luciferase-encoding plasmid DNA, and they can act as a protein expression enhancer. Interestingly, the peptides additionally exhibited strong antimicrobial activity against the enterobacterium