Cationic Liposomes in Different Structural Levels for Gene Delivery

Abstract

Over the last few decades, as a promising strategy for the treatment of many refractory diseases, such as inherited diseases (Martin-Rendon & Blake, 2003) and acquired immunodeficiency syndrome (AIDS) (Fanning et al., 2003), gene therapy, the objective to allow a gene to express the protein coded in the target cells and consequently to treat disease by the protein secreted from cells transfected, has become an invaluable experimental tool to study gene function and its regulation (El-Aneed, 2004). The success of gene therapy critically depends on suitable transfection vectors, which have the high efficiency transfer of genes to target cells as well as a favorable safety profile. Broadly, these vectors are mainly classified into two categories: viral and non-viral (Liu & Huang, 2002). Currently, viral vectors based on many different viruses such as adenovirus and retrovirus have achieved some success particularly in cancer gene therapy (Williams et al., 2010), and their performance and pathogenicity have been evaluated in animal models. However, several issues including difficulty in production, limited opportunity for repeated administrations due to acute inflammatory response, and delayed humeral or cellular immune responses need to be addressed, so that their clinical potential can be fully realized (Love et al., 2010). Thus it is necessary to develop more efficient and flexible security system in the category of vectors for gene delivery. Synthetic non-viral vectors are potential alternatives to viral vectors, and may help to overcome some of these problems (Zhang et al., 2010). Among these, cationic compounds (mainly including cationic lipids and cationic polymers) are believed to cause less safety problems due to their relative simplicity, and have been the most extensively studied. Since the first description of successful in vitro transfection with cationic lipid by Felgner et al. in 1987 (Felgner et al., 1987), numerous cationic lipids have been synthesised and used for delivery of nucleic acids into cells during the last 20 years. Cationic liposomes are composed of lipid constituents, and have improved the gene delivery efficacy owing to their typical bilayer structure. Some helper lipids such as dioleylphosphatidyl choline (DOPC) or dioleylphosphatidyl ethanolamine (DOPE), typically neutrally lipids (Zuhorn et al., 2005), are often employed with cationic lipids, and play very important role during the formation of lipoplexes by combining cationic liposomes and genes, as they could determine the morphologies of lipoplexes.