Pharmacokinetic and pharmacodynamic considerations in gene therapy

被引:99
|
作者
Kamiya, H [1 ]
Akita, H [1 ]
Harashima, H [1 ]
机构
[1] Hokkaido Univ, Grad Sch Pharmaceut Sci, Lab Mol Design Pharmaceut, Kita Ku, Sapporo, Hokkaido 0600812, Japan
关键词
D O I
10.1016/S1359-6446(03)02889-7
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
During gene therapy the concentration of plasmid DNA or oligonucleotides in the plasma can be quite different from their concentrations in the nucleus or cytosol where they exert their actions. For a better understanding of the apparent discrepancies between pharmacokinetics (PK) and pharmacodynamics (PD), a new concept for intracellular PK with an emphasis on the final efficacy of gene transcription is needed. Here, the conventional PK and intracellular PK and PD of non-viral gene delivery systems are discussed, together with a new concept, referred to as controlled intracellular disposition, which integrates these factors to gain a better understanding of gene expression in the nucleus. The importance of optimizing the system from a transcriptional point of view in the nucleus is also discussed. These new concepts must be integrated to develop an optimized non-viral gene delivery system.
引用
收藏
页码:990 / 996
页数:7
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