| Literature DB >> 27574785 |
Yuji Kobayashi1, Kenya Kamimura1, Hiroyuki Abe1, Takeshi Yokoo1, Kohei Ogawa1, Yoko Shinagawa-Kobayashi1, Ryo Goto1, Ryosuke Inoue1, Masato Ohtsuka2,3, Hiromi Miura4, Tsutomu Kanefuji1, Takeshi Suda1, Masanori Tsuchida5, Yutaka Aoyagi1, Guisheng Zhang6, Dexi Liu6, Shuji Terai1.
Abstract
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.Entities:
Year: 2016 PMID： 27574785 PMCID： PMC5023407 DOI： 10.1038/mtna.2016.63
Source DB: PubMed Journal: Mol Ther Nucleic Acids ISSN： 2162-2531 Impact factor: 10.183