Gene Therapy Using Dc-Chol Liposomes

Gene therapy offers the potential to deliver genetic material inside the cells for correcting a disease phenotype. Various techniques for the transgene delivery have been developed, among which cationic liposome mediated delivery is widely acceptable. DC-Chol/DOPE cationic liposomes, synthesized in our laboratory, have several alluring features such as low toxicity, non-immunogenicity, ease of utilization and stability. These liposomes have been successfully used as a vector in clinical trials for treating melanoma and cystic fibrosis. Only a small portion of the DNA-liposome complex taken up by the cell is eventually available for gene expression in the nucleus. To overcome the problem of limited expression, we have developed a cytoplasmic expression system in which the reporter gene is placed under the control of a bacteriophage T7 promoter. To initiate the expression of the gene either purified T7 RNA polymerase or T7 autogene expression vector is transfected along with the reporter gene. Prolonged transgene expression was observed in tumor cells treated with this novel gene transfer system. In an effort to enhance the transgene expression in vivo, we discovered that injections of cisplatin into tumor-bearing mice prior to injecting the DNA-liposome complex significantly enhances the transgene expression. A sequential, combination therapy protocol is therefore proposed for cancer gene therapy.