Non-viral gene therapy: synthesis, characterization and transfection studies of site-targeted nanocarriers based on biocompatible polycations

Abstract

The treatment of diseases by means of gene therapy is becoming a reality, specially due to the massive investment on fundamental research about the understanding of the transfection mechanism and the barriers. The latter prevents effective steps of carrying, delivery and expression of genes. Among the vectors employed for this purpose the non-viral ones are very promising due to their greater safety. However, for the treatment to become a reality, the improvement of the carrier properties is a crucial step to create an effective therapy. The hemocompatibility of the carriers and the effective delivery of genes to inside of the targeted cells are both fundamental for the gene expression to be viable. Recently, studies carried out in our group showed that phosphorylcholine-modified chitosans allowed obtaining nanoparticles with improved colloidal stability under physiological conditions, moreover the strength of interaction with DNA could be decreased, thus allowing DNA delivery. Beside these improved properties, the nanoparticles remained stable for weeks after the preparation. In this project our aim is to obtain site-targeted nanocarriers able to transfect specific cells efficiently. The project involves the synthesis and characterization of new derivatives using biocompatible polycations as starting materials, followed by studies of citotoxicity and transfection in vitro. These studies will be carried out aiming to, in a comparative way, evaluate how structural changes in the polycations chains affect the transfection efficiency in vitro, which would permit identifying the most promising system for in vivo studies. (AU)