Degradable polyethylenimines as gene carriers

Abstract

Gene therapy is a powerful treatment for inborn and acquired diseases. The development of safe and effective gene delivery systems is a great challenge to make the human gene therapy a reality. Viral vectors have been commonly employed due to the high transfection efficiency, however, their application to the human body is often frustrated by immunogenicity, potential infectivity, complicated production, and inflammation. Non-viral vectors have been widely proposed as safer alternatives to viral vectors by reason of unique advantages such as less immune reaction against repeated administration, ease of synthesis, cell/tissue targeting, unrestricted plasmid size, and low cost. Among non-viral systems, cationic polymers have gained increasing attention because they can easily form self-assembly with DNA. Polyethylenimine (PEI) is one of the most popular cationic polymers investigated in non-viral gene therapy due to its ability to generate elevated levels of gene expression in vitro and in vivo compared to another non-viral carriers. However, the PEI showed high cytotoxicity, which depends on the molecular weight of the PEI. Recently, the degradable PEIs were synthesised to have high transfection efficiency with low cytotoxicity. The present review describes recent progress on the development of degradable PEIs as non-viral vectors. The present paper also summarises structure of degradable PEIs–transfection relationship to provide a novel insight with respect to this type of gene delivery system. First, linear degradable polymers based on linear PEIs are represented. Second, branched polymers based on branched PEIs are discussed. Third, grafted degradable copolymers based on branched PEIs are explained.