The simplest way of a non-viral gene delivery system is by using a naked vector DNA. Direct injection of DNA into a cell or tissue produces high levels of gene expression. Though it leads to gene expression but level of expression is much lower than with either viral or liposomal vectors. It is unsuitable for systemic administration due to the presence of serum nuclease. Therefore its application is limited to muscle cells and skin. However the efficiency of DNA injection in the muscle injection is variable. In spite of huge amount of research, the efficiency of DNA injection in muscle has not proved efficient enough to go for the clinical level. Several researchers have shown that the naked DNA can be efficiently delivered to cells by various means such as electroporation and intravenous injection. It is particularly applied to cancer tissues where the DNA can be injected either directly into the tumor or can be injected into muscle in order to express tumor antigens that might function as a cancer vaccine. It can also be used to treat genetic diseases in the tissues which are available for direct injection such as skin.

21.1 Progress in naked DNA based gene delivery

Naked DNA is generally introduced into a muscle cell by transfection in vivo which allows the enhance uptake of DNA into muscle and skin. Intravenous delivery of plasmid DNA results in a high gene transfer to liver cells. Plasmid DNA (pDNA) delivery to tail vein is another simple and effective way of transfecting liver cells in rodents. Effective transfection of skeletal muscle cells in rodents, canines, and monkey is achieved via intravenous delivery of plasmid DNA. Many commercial pDNA expression vectors allows high-level sustained expression of DNA into different organs. The mechanism of intravenous DNA delivery is thought to involve active pDNA uptake by a targeted cell. Naked DNA delivery has now entered into many clinical trials, for eg in treatment of peripheral arterial occlusion disease. Small interfering RNA can be delivered very efficiently by intravenous route and results in silencing of targeted gene expression.

21.2 Mechanism of action of naked DNA

The plasmid DNA after injection or electroporation crosses the cell membrane. The DNA needs to go inside the nucleus in order to transcribe the mRNA by using RNA polymerase II which further migrates to cytoplasm for protein synthesis. The transfer of the DNA to nucleus is facilitated by nuclear pore.