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非ウイルス性ベクターによる臓器・部位・細胞選択的遺伝子導入法に関する研究


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タイトル: 非ウイルス性ベクターによる臓器・部位・細胞選択的遺伝子導入法に関する研究
その他のタイトル: Organ-, region- and cell-selective gene transfer using non-viral vectors
著者: 麓, 伸太郎
著者(別表記) : Fumoto, Shintaro
発行日: 2009年 9月
出版者: (社)日本薬学会
引用: YAKUGAKU ZASSHI, 129(9), pp.1055-1061; 2009
抄録: Safety in gene therapy is an important issue since both viral and non-viral vectors have toxic side effects. Not only vectors themselves, but also distributions of produced proteins affect safety in gene therapy; thus, development of target-selective gene transfer methods is rational. We have developed organ-, region- and cell-selective gene transfer methods using non-viral vectors. To deliver foreign gene to liver parenchymal cells (hepatocytes), galactosylation of cationic liposome/plasmid DNA complex is useful strategy. Based on analyses for intrahepatic disposition characteristics and interaction with blood components, we formulated novel galactosylated lipoplex with regulated salt concentration to reduce particle size of lipoplex and to stabilize lipoplex simultaneously; as a consequence, we succeeded in improvement of hepatocyte-selective gene transfer after intraportal injection of the lipoplex in mice. On the other hand, administration routes are important for target-selective gene transfer. We discovered that simple instillation of naked plasmid DNA onto organ surface (the liver, kidney, spleen, stomach and lung) in mice and rats could result in effective and region-selective transgene expression. Neither physical force nor carriers are necessary for gene transfer onto organ surface mesothelial cells. To rationally improve transfection efficiency, mechanism of gene transfer should be elucidated. We clarified that Rac-mediated macropinocytosis was required for naked plasmid DNA transfer in gastric mesothelial cells.
キーワード: Gene delivery / Gene therapy / Intraperitoneal organ / Mechanism of transfection / Targeting
URI: http://hdl.handle.net/10069/22302
ISSN: 00316903
DOI: 10.1248/yakushi.129.1055
権利: © 2009 The Pharmaceutical Society of Japan.
資料タイプ: Journal Article
原稿種類: publisher
出現コレクション:110 学術雑誌論文

引用URI : http://hdl.handle.net/10069/22302

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