Augmenter of Liver Regeneration Gene Therapy Using a Novel Minicircle DNA Vector Alleviates Liver Fibrosis in Rats.
Augmenter of Liver Regeneration Gene Therapy Using a Novel Minicircle DNA Vector Alleviates Liver Fibrosis in Rats.
复制标题
使用新型小环 DNA 载体增强肝脏再生基因疗法可减轻大鼠肝纤维化。
DOI：
10.1089/hum.2016.006
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发表时间：
2016-11
期刊：
影响因子：
--
通讯作者：
Kong X
中科院分区：
文献类型：
--
作者：
Wu X;Liu G;Mu M;Peng Y;Li X;Deng L;Zhang Z;Chen M;You S;Kong X
肝纤维化导致肝硬化、肝癌和肝功能衰竭，这是全世界死亡的主要原因。基因治疗是一种相对较新的医学模式，具有巨大的治疗潜力。开发一种高效、安全的载体系统是临床基因治疗的关键。本研究探讨了一种新型微环载体（MC-hALR）介导的肝再生增强因子/生长因子ERV 1样（ALR/GFER）基因的治疗作用。在肝纤维化大鼠中通过基于流体动力学的转染（HBT）接受MC-hALR 8周的结果表明，微环DNA载体产生比传统质粒（pcDNA3.1-hALR）更有效的基因治疗效果。即使我们将MC-hALR的治疗剂量降低到30%（w/w），治疗频率从每周一次降低到每两周一次，体外和体内结果仍然表明，较高的ALR基因表达显著抑制转化生长因子-β1（TGF-β1）、血小板衍生生长因子-BB（PDGF-BB）和α-平滑肌主动脉（α-SMA）水平的升高;有效抑制胶原尤其是I型胶原的生成，有效减轻大鼠肝损伤和纤维化，从而提高肝纤维化大鼠的存活率。初步认为MC-hALR的相对过表达抑制了肝星状细胞（HSC）的活化，从而减轻了大鼠肝纤维化。
Liver fibrosis results in cirrhosis, liver cancer, and liver failure, which is a major cause of mortality worldwide. Gene therapy is a relatively new paradigm in medicine, with enormous therapeutic potential. The development of an efficient and safe delivery system is essential for clinical gene therapy. In the present study, we evaluated augmenter of liver regeneration/growth factor ERV1-like (ALR/GFER) gene therapeutic effect mediated by a novel minicircle vector (MC-hALR). The results in liver fibrotic rats that received MC-hALR through hydrodynamics-based transfection (HBT) for 8 weeks indicated that the minicircle DNA vector produced a more effective gene therapy effect than traditional plasmids (pcDNA3.1-hALR). Even when we reduced the treatment dose of MC-hALR to 30% (w/w) and the treatment frequency from weekly to biweekly, the in vitro and in vivo results still demonstrated that higher ALR gene expression significantly blocked increases in transforming growth factor-β1 (TGF-β1), platelet derived growth factor-BB (PDGF-BB), and α-smooth muscle aorta (α-SMA) levels; effectively suppressed the production of collagens, especially collagen I; and effectively alleviated liver injury and fibrosis in rats, thereby improving the survival rate of liver fibrotic rats. It is preliminarily concluded that the relative overexpression of MC-hALR inhibits the activation of hepatic stellate cells (HSCs), thereby alleviating liver fibrosis in rats.
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DOI：
10.1038/mtna.2013.67
发表时间：
2014-01-07
期刊：
Molecular therapy. Nucleic acids
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.7
作者：
Giorda, R;Hagiya, M;Trucco, M
通讯作者：
Trucco, M
DOI：
10.1056/nejm199306243282508
发表时间：
1993-06
期刊：
The New England Journal of Medicine
影响因子：
--
作者：
S. Friedman
通讯作者：
S. Friedman
影响因子：
12.4
作者：
Chen, Zhi-Ying;Riu, Efren;Kay, Mark A.
通讯作者：
Kay, Mark A.
DOI：
10.1016/j.bbrc.2010.11.083
发表时间：
2011-01-07
影响因子：
3.1
作者：
Ilowski, Maren;Kleespies, Axel;Thasler, Wolfgang E.
通讯作者：
Thasler, Wolfgang E.