The hydrodynamics-based procedure for controlling the pharmacokinetics of gene medicines at whole body, organ and cellular levels.
Hydrodynamics-based gene delivery, involving a large-volume and high-speed intravenous injection of naked plasmid DNA (pDNA), gives a significantly high level of transgene expression in vivo. This has attracted a lot of attention and has been used very frequently as an efficient, simple and convenient transfection method for laboratory animals. Until recently, however, little information has been published on the pharmacokinetics of the injected DNA molecules and of the detailed mechanisms underlying the efficient gene transfer. We and other groups have very recently demonstrated that the mechanism for the hydrodynamics-based gene transfer would involve, in part, the direct cytosolic delivery of pDNA through the cell membrane due to transiently enhanced permeability. Along with the findings in our series of studies, this article reviews the cumulative reports and other intriguing information on the controlled pharmacokinetics of naked pDNA in the hydrodynamics-based gene delivery. In addition, we describe various applications reported so far, as well as the current attempts and proposals to develop novel gene medicines for future gene therapy using the concept of the hydrodynamics-based procedure. Furthermore, the issues associated with the clinical feasibility of its seemingly invasive nature, which is probably the most common concern about this hydrodynamics-based procedure, are discussed along with its future prospects and challenges.
Kobayashi
Naoki
N
Department of Biopharmaceutics and Drug Metabolism, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
Nishikawa
Makiya
M
Takakura
Yoshinobu
Y
D000818:Animals; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000235:genetics* / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology
D004247:DNA