Non-viral vectors in cancer gene therapy: principles and progress

This review focuses on the use of synthetic (non-viral) delivery systems for cancer gene therapy. Therapeutic strategies such as gene replacement/mutation correction, immune modulation and molecular therapy/'suicide' gene therapy type approaches potentially offer unique and novel ways of fighting cancer, some of which have already shown promise in early clinical trials. However, the specific and efficient delivery of the genetic material to remote tumors/metastases remains a challenge, which is being addressed using a variety of viral and non-viral systems. Each of these disparate systems has distinct advantages and disadvantages, which need to be taken into account when a specific therapeutic gene is being used. The review concentrates on particulate gene delivery systems, which are formed through non-covalent complexation of cationic carrier molecules (e.g. lipids or polymers) and the negatively charged plasmid DNA. Such systems tend to be comparatively less efficient than viral systems, but have the inherent advantage of flexibility and safety. The DNA-carrier complex acts as a protective package, and needs to be inert and stable while in circulation. Once the remote site has been reached the complex needs to efficiently transfect the targeted (tumor) cells. In order to improve overall transfection specificity and efficiency it is necessary to optimize intracellular trafficking of the DNA complex as well as the performance after systemic administration. Common principles and specific advantages or disadvantages of the individual synthetic gene delivery systems are discussed, and their interaction with tumor-specific and generic biological barriers are examined in order to identify potential strategies to overcome them.