Polyplex nanoparticles for gene therapy: polysaccharides and novel elastinlike polypeptide-based nanovectors development and prospects

L. M. Bravo-Anaya1,2, M. Rinaudo3, B. Garbay1,2, E. Garanger1,2, S. Lecommandoux1,2
1 University of Bordeaux, LCPO, UMR 5629, F-33600, Pessac, France
2 CNRS, LCPO, UMR 5629, F-33600, Pessac, France
3 Biomaterials applications, 6 rue Lesdiguières. 38000, Grenoble, France
Nanomedicine is holding tremendous hope in the fields of gene delivery and cancer therapy. One aim of gene therapy is to introduce a normal copy of a given gene to defective cells in order to restore an impaired biological function. Gene transfer principle relies on the use of natural or synthetic DNA complexing agents, referred to as vectors or gene carriers, that are able to compact and protect the genetic material from degradation in biological fluids and to transport it through the target cell membranes for integration into the transcription machinery of a target cell. Nowadays, cationic polymers, which interact electrostatically with negatively charged DNA forming polyplexes, are amongst the most studied non-viral gene delivery vectors. Only few natural polycations possess the characteristics favorable for gene delivery, such as low immunogenicity, biocompatibility and minimal cytotoxicity. Chitosan in particular, which is the most important derivative of chitin, is a polysaccharide that has been identified as a safe and efficient cationic carrier possessing suitable aforementioned characteristics, and the ability to protect DNA from degradation by nucleases. DNA/chitosan electrostatic complex stoichiometry, net charge, dimensions, conformation and thermal stability have been extensively studied. Furthermore, the development of innovative protein polymer nanovectors, resulting from the complexation of positively charged elastin-like polypeptides (ELPs) and DNA was recently proposed. ELPs engineering, which allows controlling several characteristics such as temperature responsiveness, biocompatibility, cell-adhesion functions, among others, is currently explored to design DNA/ELPs nanoparticles and considered as an attractive alternative delivery system for improving the efficiency of gene therapies.
Summary of academic career
Dr. Lourdes Mónica Bravo Anaya received her PhD degree in Chemical Engineering and in Fluid Mechanics, Processes and Energy in 2015 prepared under the collaboration between the University of Guadalajara (México) and the University of Grenoble (France). Now, she is working as a Post-Doc in the group of “Polymer Self-Assembly and Life Sciences”, leaded by Pr. Sébastien Lecommandoux at the LCPO (Laboratoire de Chimie des Polymères Organiques, Bordeaux, France). Her current research interests include the study of adsorption processes of nucleic acids through electrochemical methods; the study of physical-chemical and rheological properties of polyelectrolyte such as DNA in aqueous solutions; physical-chemical properties and applications of polysaccharides and polypeptides; the study of DNA diluted and entangled solutions dynamics; DNA and RNA complexation process through electrostatic interactions, polysaccharide and elastin-based nanoparticles development for gene therapy. Dr. Mónica Bravo is recipient of the Science and Technology Award Jalisco 2016 (México) and over 6 awards at national and international conferences (Best poster awards and travel awards). Up to now, she has presented over 15 oral presentations in international conferences and has published 11 research articles in international journals. She is member of the National System of Researchers of México, member of the ISE (International Society of Electrochemistry) and member of the GFR (Groupe Français de Rhéologie).