Biol. Pharm. Bull. 28(4) 701—706 (2005)

many diseases, has some potential for the treatment of certain types of serious cancer such as lung cancer. During the past 15 years, more than 400 clinical studies in gene therapy have been evaluated and almost 70% of these studies were in the area of cancer gene therapy. However, even though much clinical research has been carried, the validity of this treatment has not been confirmed. The key for successful gene therapy in the treatment of cancer is the technology used for gene delivery, in which targeted gene delivery to a tumor is achieved. For this purpose, many studies have been directed toward the development of a useful vector system. Vectors for gene therapy can be categorized into two groups: viral and non-viral vectors. The viral vectors mimic the properties of viruses that naturally infect cells and transfer their genetic materials, resulting in a highly efficient gene transfer. They have, however, some limitations which include difficulty for production and toxicity (in particular immunogenecity). Non-viral vectors based on (poly)cationic lipids, liposomes, and polymers form negatively charged natural and synthetic DNA. It is generally believed that the positive charge on the vector/DNA complex ensures its binding to the cell membrane because of the negative charge on the cell membrane and it then enters the target cells. Although the gene transfer efficiency of non-viral vectors is less than that of their viral counterparts and is also transient in nature, these systems are likely to present several advantages including low-cost and large-scale production, safety, lower immunogenecity, and the capacity to deliver large gene fragments. A cationic liposome, TFL-3, composed of a cationic lipid, DC-6-14, with helper lipids dioleoylphosphatidylethanolamine (DOPE) and cholesterol (CHOL), showed a higher lipofection efficiency in dividing or non-dividing cells in vitro, even in the presence of serum and in vivo. Generally, gene fragments in complexes formed with non-viral vectors are easily and quickly degraded in the presence of serum. An electron microscopic study showed that gene fragments/TFL-3 complexes (lipoplexes) retained their morphology in the presence of serum. This may account for the high gene transfer activity in serum-containing media and in vivo. Based on the above discussion, TFL-3 would be expected to be a superior non-viral vector that could be systemically injected. In vivo lipofection, the transgene expression would occur as a function of the distribution of the lipoplexes. In addition to the physicochemical properties of the component lipids, the colloidal properties of lipoplexes such as their stability in plasma, pharmacokinetics and biodistribution are major determinant factors achieving the highest transgene and tissue specific expressions. Organ distribution can be modulated by varying the lipid-to-pDNA ratio or the size of the lipoplexes. With the aging of society in the 21st century, the incidence of cancer is expected to increase. The morbidity rate of lung cancer has been rising particularly rapidly, and a pressing countermeasure is necessary. Lipoplexes usually accumulate largely in the lung, although the distribution changes with time: lipoplexes are found in the lung shortly after intravenous injection but eventually accumulate in the liver after 24 or 48 h. This is because the lipoplex form aggregates in the blood stream, and is captured in the first capillary enApril 2005 Biol. Pharm. Bull. 28(4) 701—706 (2005) 701