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当前基因载体的细胞内转导、代谢和毒性。

Intracellular trafficking, metabolism and toxicity of current gene carriers.

机构信息

Institute of Biomedical Engineering, National Taiwan University, Taipei, Taiwan.

出版信息

Curr Drug Metab. 2009 Oct;10(8):885-94. doi: 10.2174/138920009790274504.

Abstract

Gene delivery remains to be a very challenging field to efficiently transport the therapeutic gene and to modulate proteins with the desired function at the target site. The physiochemical and biological barriers are the major hurdles that need to be considered, particularly when administered systematically, in order to optimize the therapeutic efficacy. Numerous modifications have been extensively investigated aiming to provide protection from the plasma degradation, enhancement of transfection, target specificity, and most importantly, minimizing the side effects such as cellular toxicity and immune response. This article provides a review with respect to the in vitro and in vivo toxicity, as well as cellular and physiological interactions with the gene delivery system composed from viral vectors, cationic lipids and polymers. Recent progress and development are also addressed, with promising results that may be further adopted for clinical use.

摘要

基因传递仍然是一个极具挑战性的领域,需要有效地将治疗基因输送到靶位,并调节具有所需功能的蛋白质。生理化学和生物学屏障是需要考虑的主要障碍,特别是在系统性给药时,以优化治疗效果。为了提供对血浆降解的保护、增强转染、靶向特异性,以及最重要的是最小化细胞毒性和免疫反应等副作用,已经广泛研究了许多修饰方法。本文综述了病毒载体、阳离子脂质体和聚合物组成的基因传递系统的体外和体内毒性,以及与细胞和生理相互作用。还讨论了最近的进展和发展,有希望的结果可能会进一步应用于临床。

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