pH敏感基因载体的研究现状

doi:10.6023/A12110974

摘要/Abstract

基因治疗正成为遗传病、癌症等疾病的有效治疗方法. 基因治疗实现的最大挑战是开发安全有效的基因运载载体以将目的基因从血液运送到细胞质或细胞核. 目前, 常用的基因治疗载体有病毒载体和非病毒载体. 非病毒载体由于安全性好, 易于合成, 易于修饰而得到了更为广泛的研究. 其中pH敏感载体作为功能性非病毒载体, 不仅安全性高, 而且有更好的体内基因转染效率, 为非病毒性载体在临床上的应用开辟了广阔的前景. 本文主要从pH敏感脂质和pH敏感聚合物两方面对pH敏感基因载体进行简要综述, 介绍了该两类载体的构建方法及其对基因的运载机制.

关键词: 基因治疗, 基因传递, 非病毒基因载体, pH敏感脂质体, pH敏感聚合物

Gene therapy shows promise as a potentially revolutionizing strategy for treatment of many genetically-related diseases, such as cancer. However, the lack of safe and effective gene delivery carriers (or vectors) has become a bottleneck in its basic research and clinical application. Generally, gene delivery carriers can be divided into viral and non-viral ones. Although non-viral gene delivery carriers can offer some advantages such as safety and facile fabrication, they don't possess the same high gene delivery efficiency as viral gene delivery carriers do, due to lack of functionality to overcome many intracellular gene-delivery obstacles. Currently, many kinds of "smart" non-viral gene-delivery carriers have been developed in order to realize efficient gene-delivery, since such carriers can undergo physical or chemical reactions in response to changes in pH, oxidative state, or enzymatic activity. As these stimuli or cues may be specific to a biological site, tissue, or condition, it may facilitate the release of the nucleic acid cargo at the desired site in an efficient manner. Among all these stimuli-responsive carriers, pH-responsive one has attracted major attention and great impetus has been directed towards utilizing the subtle yet significant change in pH value within the cellular compartments. In this review, we give an overview of pH-sensitive lipids and polymers which have been designed and developed in recent years, with focus on their structural features and consequent functional attributes to achieve efficient transfection. The underlying modes of actions relating to structure and differential pH environment have also been discussed. It is worthy to note that despite many pH-sensitive carriers have shown success in vitro and a few in vivo, none have entered clinical phase for their transfection activity is still insufficient. To develop more efficient gene delivery carriers, the exact mechanisms of how these pH-sensitive carriers overcome each intracellular obstacle, as well as some concepts such as "proton sponge", have to be maken more clear or verified further.

Key words: gene therapy, gene delivery, nonviral gene carrier, pH-sensitive lipids, pH-sensitive polymers

引用此文

沈银, 胡桂香, 张华星, 齐莉莉, 骆成才. pH敏感基因载体的研究现状[J]. 化学学报, 2013, 71(03): 323-333.

Shen Yin, Hu Guixiang, Zhang Huaxing, Qi Lili, Luo Chengcai. Recent Progress in pH-Sensitive Gene Carriers[J]. Acta Chimica Sinica, 2013, 71(03): 323-333.

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