著者

中西 秀之 樋口 ゆり子 川上 茂 山下 富義 橋田 充

出版者

公益社団法人 日本薬学会

雑誌

YAKUGAKU ZASSHI (ISSN:00316903)

巻号頁・発行日

vol.129, no.12, pp.1433-1443, 2009-12-01 (Released:2009-12-01)

参考文献数

58

被引用文献数

3 3

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Transposons are mobile genetic elements that move between or within vectors and chromosomes. For the transposition, an enzyme called transposase recognizes transposon-specific terminal inverted repeat sequences (IRs) located on both ends of transposons, and remove them from their original sites and, integrates them into other sites. Because of this feature, transposons containing genes of interest between their two IRs are able to carry the genes from vectors to chromosomes. Transposons are promising systems for chromosomal integration because they can not only integrate exogenous genes efficiently, but also be transfected to a variety of cells or organs using a range of transfection methods. In this review, we focused on the therapeutic application of transposons. A few transposons can integrate transgenes into mammalian chromosomes. They have been used in preclinical studies of gene therapy and cell therapy. In addition, they have recently been used for generation of induced pluripotent stem cells. Transposon-based integrative vector systems have two components. One is the transposon containing transgenes, and the other is the expression cassette of the transposase. Both viral and non-viral vectors have been used to deliver these two components to mammalian cells or organs, and sustained transgene expression has been achieved. Transposon-mediated sustained transgene expression has also produced therapeutic effect in disease models of hereditary and chronic diseases. Although transposon-based integrative vector systems have problems, such as insertional mutagenesis, studies to overcome these problems have been progressing, and these vector systems will become indispensable tools to cure refractory diseases.

著者

橋田 充 山下 富義 西川 元也 川上 茂

出版者

京都大学

雑誌

特定領域研究

巻号頁・発行日

2005

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癌細胞の動態、存在状態の多様性および治療薬の癌病巣への到達性の制御の困難さのため、普遍的に適用可能な治療法は未だ確立されていない。本研究では、まず、癌増殖・転移過程の非侵襲的解析に必要不可欠な基盤技術であるバイオイメージングによる可視化および定量法を確立した。さらに、DDSのコンセプトに基づき、有効な癌治療薬および遺伝子医薬品の送達システムの開発および治療への応用を行った。

著者

高倉 喜信 藤田 卓也 橋田 充 瀬崎 仁

出版者

日本DDS学会

雑誌

Drug Delivery System (ISSN:09135006)

巻号頁・発行日

vol.3, no.3, pp.405-409, 1988-10-01 (Released:2009-02-23)

参考文献数

12

被引用文献数

1 1

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The disposition and tumor localization of model macromolecules with the same molecular weight but different electric charge were studied in sarcoma 180 bearing mice. Dextran (T-70) with molecular weight of 70, 000, cationic DEAE-dextran (T-70), anionic CM-dextran (T-70), bovine serum albumin(BSA), and cationized BSA (cBSA)were injected intravenously and their tissue distribution was determined by radioactivity counting. The cationic macromolecules were rapidly cleared from plasma and accumulated in the liver, and spleen or excreted into urine, while tumor levels remained low. On the contrary, anionic macromolecules were retained in the plasma for a long time and slowly accumulated to the tumor. The present study revealed that macromolecules having an anionic charge are advantageous for tumor targeting.