具体交货肝胶原α1（I）中的siRNA脂质纳米粒一样的解析肝纤

StephenW

Specific hepatic delivery of procollagen α1(I) siRNA in lipid-like nanoparticles resolves liver fibrosis

    Carolina Jiménez Calvente1,2, Alfica Sehgal3, Yury Popov4, Yong Ook Kim1,2, Victor Zevallos1,2, Ugur Sahin2,5, Mustafa Diken2,5 andDetlef Schuppan1,2,4,*

DOI: 10.1002/hep.27936

© 2015 by the American Association for the Study of Liver Diseases

Issue
Vol. 61 Issue 6
Hepatology

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)
Article has an altmetric score of 4

    1    Institute of Translational Immunology, University of Mainz Medical Center, Mainz, Germany
    2    Research Center for Immunotherapy (FZI), University of Mainz Medical Center, Mainz, Germany
    3    Alnylam Pharmaceuticals, Cambridge, USA
    4    Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, USA
    5    Center of Translational Oncology (TRON), Mainz, Germany

*Corresponding author: Detlef Schuppan, Institute of Translational Immunology, University Medical Center, Johannes Gutenberg University, Langenbeckstraße 1, 55131 Mainz, Germany. Tel: +49-6131-177356, Fax: +49-6131-177357. Email: [email protected]


    collagen;fibrosis;myofibroblast;nanoparticle;siRNA

Abstract

Fibrosis accompanies the wound-healing response to chronic liver injury and is characterized by excessive hepatic collagen accumulation dominated by collagen type I that often progresses to cirrhosis. Here we present ample in-vivo evidence of an up to 90% suppression of procollagen α1(I) expression, a reduction of septa formation and a 40-60% decrease of collagen deposition in mice with progressive and advanced liver fibrosis, that received cationic lipid nanoparticles loaded with small interfering RNA to the procollagen α1(I) gene (LNP-siCol1a1). After intravenous injection up to ninety percent of LNP-siCol1a1 were retained in the liver of fibrotic mice and accumulated in nonparenchymal > parenchymal cells for prolonged periods, significantly ameliorating progression and accelerating regression of fibrosis. Conclusion: The data reported in the present study extensively show that LNP-siCol1a1 specifically reduce total hepatic collagen content without detectable side effects, potentially qualifying as a therapy for fibrotic liver diseases. This article is protected by copyright. All rights reserved.

StephenW

具体交货肝胶原α1（I）中的siRNA脂质纳米粒一样的解析肝纤维化

    卡罗来纳州希门尼斯Calvente1,2，Alfica Sehgal3，尤里Popov4，勇OOK Kim1,2，维克多Zevallos1,2，的Ugur Sahin2,5，穆斯塔法Diken2,5 andDetlef Schuppan1,2,4，*

DOI：10.1002 / hep.27936

©2015年肝病研究的美国协会

问题
卷。 61第6期
肝病

接受第（接受，未编辑的文章，并在网上公布可引用的最终编辑和记录的排版本将出现在未来。）
文章有altmetric比分4

    平移免疫，美因茨大学医学中心，美因茨，德国1研究院
    2研究中心免疫疗法（FZI），美因茨大学医学中心，德国美因茨
    3 Alnylam制药，剑桥，美国
    4科消化科，贝斯以色列女执事医疗中心，哈佛大学医学院，波士顿，美国
    转化肿瘤学杂志5中心（TRON），美因茨，德国

*通讯作者：德特勒夫Schuppan，平移免疫学，大学医​​学中心，约翰内斯·古腾堡大学，Langenbeckstraße1，55131美因茨，德国的研究所。联系电话：+ 49-6131-177356，传真：+ 49-6131-177357。电子邮件：[email protected]


    胶原蛋白;纤维化;肌成纤维细胞;纳米颗粒;的siRNA

抽象

纤维化伴随伤口愈合响应于慢性肝损伤，其特征是过度的肝胶原蓄积由I型胶原蛋白是常常发展为肝硬化为主。这里，我们提出充足的体内证据的高达90％的抑制原胶原α1（I）中的表达，减少了隔片的形成和减少胶原沉积的小鼠渐进性和晚期肝纤维化40-60％的，即接收到的阳离子的装有小干扰RNA的原胶原α1（I）的基因（LNP-siCol1a1）脂质纳米颗粒。静脉注射后多达LNP-siCol1a1的90％被保留在纤维化的小鼠的肝和非实质积累>实质细胞长时间，显著改善恶化和加速纤维化消退。结论：报告在本研究的数据广泛表明LNP-siCol1a1具体地说减少没有可检出的副作用全肝胶原蛋白含量，可能有资格作为治疗肝纤维化的疾病。这篇文章是受版权保护的。版权所有。