遺伝子医薬品のDDS開発とその問題点

抄録

Recently, DNA medicines have attracted great interest as a novel class of therapeutic agents against various kinds of inherited and acquired disorders. These medicines involves antisense oligonucleotides and plasmid DNA, which enable us to treat the diseases at gene expression level. However, the therapeutic potentials of the DNA medicines are limited due to their physicochemical and biological characteristics as nucleic acids. Therefore, it is virtualy necessary to develop desirable drug delivery systems for DNA medicines. In vivo disposition property of DNA medicines is one of the most critical issues to be considered in developing DNA delivery systems. Based upon the understanding of their in vivo disposition characteristics, rational design of delivery systems, which can realize desirable disposition profiles of DNA medicines in the body, would be possible. In this paper, we will review our pharmacokinetic studies using model oligonucleotides and plasmid DNA in order to constract the startegy for DNA delivery systems. Basic pharmacokinetic characteristics and mechanisms involved in disposition processes have been studied at whole body level in mice and at organ level employing organ perfusion experimental systems.