並列タイトル等Effects of Fibrotic Tissue on Liver-targeted Hydrodynamic Gene Delivery.
肝臓選択的ハイドロダイナミック遺伝子導入法において、線維組織が導入効率に与える影響
一般注記Hydrodynamic gene delivery is a common method for gene transfer to the liver of small animals, and its clinical applicability in large animals has been demonstrated. Previous studies focused on functional analyses of therapeutic genes in animals with normal livers and little, however, is known regarding its effectiveness and safety in animals with liver fibrosis. Therefore, this study aimed to examine the effects of liver fibrosis on hydrodynamic gene delivery efficiency using a rat liver fibrosis model. We demonstrated for the first time, using pCMV-Luc plasmid, that this procedure is safe and that the amount of fibrotic tissue in the liver decreases gene delivery efficiency, resulting in decrease in luciferase activity depending on the volume of fibrotic tissue in the liver and the number of hepatocytes that are immunohistochemically stained positive for transgene product. We further demonstrate that antifibrotic gene therapy with matrix metalloproteinase-13 gene reduces liver fibrosis and improves efficiency of hydrodynamic gene delivery. These results demonstrate the negative effects of fibrotic tissue on hydrodynamic gene delivery and its recovery by appropriate antifibrotic therapy
学位の種類: 博士（医学）. 報告番号: 甲第4252号. 学位記番号: 新大院博（医）甲第730号. 学位授与年月日: 平成29年3月23日
Molecular Therapy. Nucleic Acids 5(8) e359 2016
新大院博（医）甲第730号
元資料の権利情報 : © 2016 Elsevier Inc. All rights reserved
DOIinfo:doi/10.1038/mtna.2016.63
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