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Structural and biological evaluations of polyplexes obtained by the complexation of DNA and polyethylenimine derivatives containing alkyl chains and lactose towards the treatment of genetic eye disorders

Grant number: 19/12944-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2020
Effective date (End): February 29, 2024
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
Principal researcher:Fernando Carlos Giacomelli
Grantee:Fernando Augusto de Oliveira
Home Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil


This proposal aims at the development of novel non-viral vectors for gene therapies for ocular diseases. It is nowadays well accepted that a number of blinding dystrophies is linked to aberrations in the retina and genetic disorders. In this framework, gene therapy has been identified as a favored candidate for such treatments since the eye is an easily accessible organ shielded from systemic circulation, thus minimizing potential unwanted side-effects. Nevertheless, gene transport into the ocular surface cell is difficult due to several physiological obstacles including blinking, tear reflex, nasolacrimal drainage and poor corneal permeability. In this regard, we wish to contribute by evaluating novel supramolecular polymeric assemblies based on derivatives of the golden transfecting agent polyethyleneimine as gene delivery platforms particularly to the human eye. The polymer-DNA polyplexes will be manufactured from hydrophobically and-or sugar-modified polyethyleneimine (PEI). We target the cellular uptake of the assemblies (evaluated by CLSM and flow cytometry) and further gene transfection into hard-to-transfect human Retinal Pigment Epithelium (RPE) cells (evaluated by luciferase gene transfection kit). The cell cytotoxicity of the polymeric supramolecular assemblies will be evaluated by MTT assay. We expect to demonstrate that the chemical nature of the complexing agents (in regard to the presence of sugar molecules and-or hydrophobic domains) remarkably influence transfection efficiency and cytotoxicity to RPE cells. Overall, we wish to contribute to solve a remarkable obstacle which is the achievement of therapeutic goals in ocular diseases. Since the number of patients with ocular problems is absolutely non-negligible, our approach is supposed to have a societal impact in people's quality of life since it is supposed to contribute to design safer and more effective nanomedicines for the future. Additionally, we highlight that this proposal is in the framework of the NanoPol Project which has been approved in Europe and receives funding from the European Union's Horizon 2020 research and innovation programme under the Marie SkBodowska-Curie Actions (MSCA) Research and Innovation Staff Exchange (RISE) H2020-MSCA-RISE-2018 Grant Agreement No 823883 (the UFABC is one of the Partner Institutions). The main objective of the NanoPol project is the creation of new knowledge in the field of polymeric drug delivery systems for ophthalmological applications. (AU)