Theoretical considerations involving the pharmacokinetics of plasmid DNA.
Success of in vivo gene therapy relies on the development of gene delivery technologies, by which a well-controlled transgene expression is achieved as far as the spatial and temporal profile of the expression is concerned. Because transgene expression only occurs in cells that are transduced with the gene administered, the tissue distribution of genes is an important factor determining the efficacy of in vivo gene transfer. Plasmid DNA is the simplest vector and its administration in naked or complexed form results in significant transgene expression in various organs. The route of administration, the use of cationic vectors and the administration technique greatly affects the tissue distribution of plasmid DNA and the subsequent transgene expression. Therefore, a clear understanding of the tissue distribution of naked and complexed plasmid DNA is a prerequisite for strategies for developing effective in vivo gene transfer methods. Pharmacokinetics translates the tissue distribution properties of plasmid DNA into quantitative parameters, which can be compared with parameters obtained under different conditions, or with physiological parameters such as blood flow rate. Here we discuss the pharmacokinetic evaluation of the tissue distribution characteristics of plasmid DNA, in the free and complexed forms.
Nishikawa
Makiya
M
Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan. makiya@pharm.kyoto-u.ac.jp
Takakura
Yoshinobu
Y
Hashida
Mitsuru
M
D000818:Animals; D004270:DNA, Circular / Q000008:administration & dosage / Q000235:genetics / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods / Q000639:trends; D018014:Gene Transfer Techniques / Q000639:trends; D006801:Humans; D008956:Models, Chemical; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics* / Q000493:pharmacokinetics*; D014018:Tissue Distribution / Q000235:genetics
D004270:DNA, Circular