Delivery approaches of gene therapy in hepatocellular carcinoma.

Gene therapy has the potential to provide therapeutic benefits to hepatocellular carcinoma (HCC) patients and has been the subject of intense pre-clinical and clinical research in recent years. In HCC, delivery of gene therapy has been attempted through multiple routes, using many vectors and genes in both animal models and patients. Unfortunately, a highly effective gene therapy for HCC has not been reported so far. The efficiency and selectivity of the gene transfer to the tumor tissue is too low. A great proportion of the failure can be attributed to the gene/vector complex itself. However, there is certainly a critical role played by the delivery technique. In the last decade a large amount of studies has been conducted to develop the ideal gene delivery technique for HCC, though questions regarding safety, repeatability, and efficiency still linger. The aim of this article is to review gene delivery techniques for HCC. It focuses on the relationship between the gene/vector complex and the delivery technique at promoting efficacy of gene therapy, without the cost of unacceptable systemic toxicity. The delivery techniques include systemic intravenous (IV) injection, intra-arterial (IA) injection, intra-tumoral (IT) injection, intra-portal (IP) injection, intra-biliary (IB) delivery and intra-splenic (IS) injection. The relative merits of each of these techniques are herein analyzed and discussed.