Technical Improvement and Application of Hydrodynamic Gene Delivery in Study of Liver Diseases.

Technical Improvement and Application of Hydrodynamic Gene Delivery in Study of Liver Diseases.
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水动力基因递送技术的改进及其在肝病研究中的应用

DOI:
10.3389/fphar.2017.00591
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发表时间:
2017
影响因子:
5.6
通讯作者:
Tian Z
Tian Z
中科院分区:
医学2区
文献类型:
--
作者:
Huang M;Sun R;Huang Q;Tian Z

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开发安全、高效的体内基因传递方法对分子生物学研究和后续基因治疗的进展是必不可少的。在过去的几年中,流体动力学基因传递(HGD)与裸DNA引起了越来越多的研究和潜在的临床应用的兴趣,由于其高效率和低风险,在引发免疫反应和致癌性相比,病毒载体。该方法涉及静脉内注射(i.v.)在短时间内大量的DNA,给出了一个短暂的,但高的体内基因表达,特别是在小动物的肝脏。除了DNA之外,它还被证明可以在体内递送其他物质,如RNA、蛋白质、合成的小化合物甚至病毒。由于HGD能够稳健地模拟体内肝内B型肝炎病毒(HBV)的产生,因此它已成为我们小组和许多其他小组研究HBV的基础和重要技术。最近,有关于该技术在其他肝脏研究中的应用和进一步改进的有趣报告。本文就流体动力学给药的原理、安全性、在肝脏疾病研究中的应用现状及发展进行综述,并对其未来的发展前景、临床潜力及面临的挑战进行探讨。
Development of an safe and efficient in vivo gene delivery method is indispensable for molecular biology research and the progress in the following gene therapy. Over the past few years, hydrodynamic gene delivery (HGD) with naked DNA has drawn increasing interest in both research and potential clinic applications due to its high efficiency and low risk in triggering immune responses and carcinogenesis in comparison to viral vectors. This method, involving intravenous injection (i.v.) of massive DNA in a short duration, gives a transient but high in vivo gene expression especially in the liver of small animals. In addition to DNA, it has also been shown to deliver other substance such as RNA, proteins, synthetic small compounds and even viruses in vivo. Given its ability to robustly mimic in vivo hepatitis B virus (HBV) production in liver, HGD has become a fundamental and important technology on HBV studies in our group and many other groups. Recently, there have been interesting reports about the applications and further improvement of this technology in other liver research. Here, we review the principle, safety, current application and development of hydrodynamic delivery in liver disease studies, and discuss its future prospects, clinical potential and challenges.
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