Effects of Fibrotic Tissue on Liver-targeted Hydrodynamic Gene Delivery.
Effects of Fibrotic Tissue on Liver-targeted Hydrodynamic Gene Delivery.
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DOI：
10.1038/mtna.2016.63
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发表时间：
2016-08-30
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水动力基因递送是小动物肝脏基因转移的常用方法，其在大型动物中的临床适用性已得到证实。之前的研究主要集中在正常肝脏动物中治疗基因的功能分析，然而，对其在肝纤维化动物中的有效性和安全性知之甚少。因此，本研究旨在利用大鼠肝纤维化模型研究肝纤维化对水动力基因传递效率的影响。我们使用 pCMV-Luc 质粒首次证明该过程是安全的，肝脏中纤维化组织的数量会降低基因传递效率，导致荧光素酶活性降低，具体取决于肝脏中纤维化组织的体积和转基因产物免疫组织化学染色呈阳性的肝细胞数量。我们进一步证明，使用基质金属蛋白酶-13基因进行抗纤维化基因治疗可减少肝纤维化并提高水动力基因递送的效率。这些结果证明了纤维化组织对水动力基因传递及其通过适当的抗纤维化治疗的恢复的负面影响。
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.
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影响因子：
3.7
作者：
Kamimura K;Kanefuji T;Yokoo T;Abe H;Suda T;Kobayashi Y;Zhang G;Aoyagi Y;Liu D
通讯作者：
Liu D
用于肝纤维化的基质金属蛋白酶基因递送。
影响因子：
3.7
作者：
Iimuro, Yuji;Brenner, David A.
通讯作者：
Brenner, David A.
影响因子：
13.5
作者：
Higashiyama, Reiichi;Inagaki, Yutaka;Okazaki, Isao
通讯作者：
Okazaki, Isao
影响因子：
12.4
作者：
Kamimura, Kenya;Suda, Takeshi;Liu, Dexi
通讯作者：
Liu, Dexi
DOI：
10.1038/mt.2009.206
发表时间：
2010-01
期刊：
Molecular therapy : the journal of the American Society of Gene Therapy
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