An overview of current delivery systems in cancer gene therapy

The main objective in gene therapy is the development of efficient, non-toxic gene carriers that can encapsulate and deliver foreign genetic materials into specific cell types such as cancerous cells. During the past two decades, enormous research in the area of gene delivery has been conducted worldwide, in particular for cancer gene therapy application. Viral vectors are biological systems derived from naturally evolved viruses capable of transferring their genetic materials into the host cells. Many viruses including retrovirus, adenovirus, herpes simplex virus (HSV), adeno-associated virus (AAV) and pox virus have been modified to eliminate their toxicity and maintain their high gene transfer capability. The limitations associated with viral vectors, however, in terms of their safety, particularly immunogenicity, and in terms of their limited capacity of transgenic materials, have encouraged researchers to increasingly focus on non-viral vectors as an alternative to viral vectors. Non-viral vectors are generally cationic in nature. They include cationic polymers such as poly(ethylenimine) (PEI) and poly(L-lysine) (PLL), cationic peptides and cationic liposomes. The newly described liposomal preparation LPD (liposomes/protamine/DNA), for example, has shown superiority over conventional liposomes/DNA complexes (lipoplexes). Although non-viral vectors are less efficient than viral ones, they have the advantages of safety, simplicity of preparation and high gene encapsulation capability. This article reviews the most recent studies highlighting the advantages and the limitations of various types of gene delivery systems used in cancer gene therapy. (C) 2003 Elsevier B.V. All rights reserved.