Structure-Activity Relationship in Non-Viral Vectors for DNA Delivery: The Case of Cell-Penetrating Peptides

Cell-penetrating peptides (CPPs) are highly promising bioactive molecules for the development of nano therapies. These species typically consist of short sequences of amino acids, ranging from 5 to 30 residues, and exhibit a strong ability to translocate across biomembranes. These remarkable features make them ideal for use in the production of non-viral vectors in various applications, including gene therapy. In addition to this application-oriented attractiveness, these architectures are also interesting model systems to investigate biomolecular self-assembly. In this communication, I will present recent studies conducted in our laboratory on the structure of DNA vectors based on CPPs [1-4]. The characteristics of different classes of CPPs will be highlighted, with special attention given to cationic sequences that easily form peptiplexes with nucleic acids and hydrophobic CPPs that exhibit low cytotoxicity and high amyloidogenic propensity [4,6]. Advanced methods for the structural characterization of these systems will be discussed, with an emphasis on small-angle scattering and atomic force microscopy-based infrared spectroscopy [5].

[1] J. Phys. Chem. B 2019, 123, 42, 8861–8871;
[2] J. Mater. Chem. B 2020,8, 2495-2507;
[3] Soft Matter 2020,16, 4746-4755;
[4] ACS Appl. Bio Mater. 2021, 4, 8, 6404–6416;
[5] J. Mol. Liq. 2022, 368, Part A, 120745;
[6] Soft Matter. 2023, 19, 4869-4879.