Pharmacokinetics of Plasmid DNA-Based Non-viral Gene Medicine.
Non-viral gene therapy can be realized by optimization of the pharmacokinetic properties of both the vector and the encoded therapeutic protein. A major obstacle to its successful clinical application is the limited ability of plasmid DNA, the most convenient gene-coding compound, to distribute within the body after in vivo administration. Under normal conditions, plasmid DNA and its non-viral vector complexes have difficulty in passing through various anatomical and biological barriers. These characteristics greatly limit the number and distribution of cells transduced with the vector, because transgene expression only occurs in cells that are reached by the vector. New approaches to the design of vectors as well as the methods of administration, such as electroporation and a hydrodynamic delivery, have increased the transgene expression in vivo, suggesting that improved distribution of plasmid DNA is possible by these approaches. In this chapter, the basic pharmacokinetic properties of naked plasmid DNA under normal conditions are first reviewed, then the properties of both naked and complexed plasmid DNA are discussed under conditions where significant transgene expression takes place.
Nishikawa
Makiya
M
Department of Biopharmaceutics and Drug Metabolism Graduate School of Pharmaceutical Sciences Kyoto University, Sakyo‐ku, Kyoto 606–8501, Japan.
Takakura
Yoshinobu
Y
Hashida
Mitsuru
M