Core-shell non-viral vectors synthesis for gene dual delivery

• Grant number: 19/13518-4
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: September 01, 2019
• End date: June 30, 2020
• Field of knowledge: Engineering - Chemical Engineering
• Principal Investigator: Lucimara Gaziola de la Torre
• Grantee: Naiara Godoi
• Host Institution: Faculdade de Engenharia Química (FEQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Associated research grant: 15/20206-8 - Modulation of monocytes, macrophages and pericytes by the colony stimulating factor genes to treat murine limb ischemia, AP.TEM

Abstract

Gene therapy is a promising technique based on genetic material delivery to cells or tissues, aiming from vaccination to treatment or slowdown in the progress of blood, immune and nervous system diseases and cancer. However, the technique success is related to gene material transportation and delivery to a specific target cell with low levels of pathogenic effects. This transfer can be performed through different nanoparticles, which is called vectors, that could be viral or non-viral. Non-viral vectors stand out for presenting less immunotoxicity, easier modeling, shorter time and cost of production. The most common non-vectors are called lipoplexes and polyplexes, which are formed by complexation of cationic liposome and cationic polymers with genetic materials, respectively. Although the advantages, one of the greatest challenges related to use of non-viral vectors is the development of system capable of reaching higher levels of gene delivery. The development of robust nanostructures, which can protect the genetic material, is an alternative to overcome this obstacle, guaranteeing nanocarrier stability and efficiency in delivering nucleic acids. In this context, this project will investigate different strategies to produce more robust non-viral vectors core-shell type to codelivery nucleic acids, also called lipopolyplexes. The core will be a polyplex formed by polyethyleneimine (PEI) and plasmid DNA. The shell will be composed of 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE), natural egg phosphatidylcholine (EPC) and 1,2-dioleoyl-3-trimethylammoniopropane (DOTAP) lipids, providing lipid bilayers to the nanocarrier, like cell membranes. Finally, core-shell nanovectors will be complexed with silencing RNA (siRNA) in the lipid shell. At the end of this project is intended to contribute to the development of different areas, such as nanotechnology and gene therapy with emphasis on gene co-delivery.