Systemic tumor-specific gene delivery.

The objective of a systemically administered cancer gene therapy is to achieve gene expression that is isolated to the tumor tissue. Unfortunately, viral systems have strong affinity for the liver, and delivery from non-viral cationic systems often results in high expression in the lungs. Non-specific delivery to these organs must be overcome if tumors are to be aggressively treated with genes such as IL-12 which activates a tumor immune response, and TNF-alpha which can induce tumor cell apoptosis. Techniques which have led to specific expression in tumor tissue include receptor targeting through ligand conjugation, utilization of tumor specific promoters and viral mutation in order to take advantage of proteins overexpressed in tumor cells. This review analyzes these techniques applied to liposomal, PEI, dendrimer, stem cell and viral gene delivery systems in order to determine the techniques that are most effective in achieving tumor specific gene expression after systemic administration.