Safety assessment of liver-targeted hydrodynamic gene delivery in dogs.
Safety assessment of liver-targeted hydrodynamic gene delivery in dogs.
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DOI：
10.1371/journal.pone.0107203
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Liu D
中科院分区：
文献类型：
--
作者：
Kamimura K;Kanefuji T;Yokoo T;Abe H;Suda T;Kobayashi Y;Zhang G;Aoyagi Y;Liu D
支持基因传递过程安全性的证据对基因治疗至关重要。先前使用基于流体动力学的程序的研究主要集中在小鼠的基因传递效率或基因功能分析。目前的研究重点是评估计算机控制和肝脏靶向水动力基因在狗体内传递的安全性，作为临床水动力基因治疗的第一步。我们证明了水动力过程的影响在注入区域是有限的，而且影响是短暂的。组织学检查和使用反射分光光度法测量肝脏微循环显示，该程序的肝脏特异性影响包括肝窦的短暂扩张。未观察到系统性损伤或毒性。生理参数，包括心电图、心率、血压、血氧饱和度和体温，在流体动力注射期间和注射后均保持在正常范围内。研究人员还检查了体重，以评估在6周内进行3次流体动力注射并间隔2周的动物的长期影响。血清生化分析显示注射后肝酶和一些细胞因子短暂升高。这些结果表明，图像引导，肝脏特异性流体动力基因传递是安全的。
Evidence in support of safety of a gene delivery procedure is essential toward gene therapy. Previous studies using the hydrodynamics-based procedure primarily focus on gene delivery efficiency or gene function analysis in mice. The current study focuses on an assessment of the safety of computer-controlled and liver-targeted hydrodynamic gene delivery in dogs as the first step toward hydrodynamic gene therapy in clinic. We demonstrate that the impacts of the hydrodynamic procedure were limited in the injected region and the influences were transient. Histological examination and the hepatic microcirculation measurement using reflectance spectrophotometry reveal that the liver-specific impact of the procedure involves a transient expansion of the liver sinusoids. No systemic damage or toxicity was observed. Physiological parameters, including electrocardiogram, heart rate, blood pressure, oxygen saturation, and body temperature, remained in normal ranges during and after hydrodynamic injection. Body weight was also examined to assess the long-term effects of the procedure in animals who underwent 3 hydrodynamic injections in 6 weeks with 2-week time interval in between. Serum biochemistry analysis showed a transient increase in liver enzymes and a few cytokines upon injection. These results demonstrate that image-guided, liver-specific hydrodynamic gene delivery is safe.
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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
影响因子：
--
作者：
通讯作者：
--
影响因子：
13.5
作者：
Huang, TP;Nishida, T;Matsuda, H
通讯作者：
Matsuda, H
影响因子：
4
作者：
Racz, Zsuzsanna;Godo, Maria;Hamar, Peter
通讯作者：
Hamar, Peter
影响因子：
12.4
作者：
Brunetti-Pierri, Nicola;Stapleton, Gary E.;Ng, Philip
通讯作者：
Ng, Philip