Polyethylenimine Derivatives as Potent Nonviral Vectors for Gene Transfer.
Polyethylenimine Derivatives as Potent Nonviral Vectors for Gene Transfer.
复制标题
聚乙烯亚胺衍生物作为基因转移的有效非病毒载体。
DOI：
10.1358/dnp.2002.15.7.840080
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发表时间：
2002
影响因子：
--
通讯作者：
G. Dolivet
中科院分区：
文献类型：
--
作者：
J. Merlin;A. N'doye;Thiefaine Bouriez;G. Dolivet
将功能性基因递送到组织中可以允许校正基因缺陷或突变，例如在严重的遗传性病理或癌症组织中观察到的那些，并且可以导致基因治疗。为了实现基因转移，主要使用病毒载体，因为它们具有进入细胞并促进转基因表达的内在能力。然而，许多因素可能限制病毒载体的使用，包括繁重的实验室基础设施，以及在反复给药的情况下，诱导针对病毒蛋白的免疫应答。已经提出了基于非病毒载体的替代基因转移技术。聚乙烯亚胺（PEI）衍生物是能够与质粒DNA形成稳定复合物的聚阳离子分子。PEI/DNA复合物附着于细胞表面，迁移成通过内吞作用进入细胞的团块，并在酸性溶酶体隔室中解聚和/或进入细胞核。PEI衍生物可以被认为是线性（22 kDa）或网状（25 kDa）分子，这些分子被证明对于体外和体内基因转移有效。除了未取代的PEI的广泛应用之外，还提出并报道了糖基化的PEI衍生物通过减小PEI/DNA复合物的尺寸和聚集来增强基因转移效率。据报道，半乳糖基化的PEI衍生物通过碳水化合物结合蛋白识别增强与细胞膜的相互作用，并将PEI/DNA复合物特异性靶向表达半乳糖凝集素的生物系统。最近，已显示葡糖基化PEI衍生物在人头颈癌肿瘤细胞中比未取代的PEI产生更高和更持久的转基因表达。本文综述了PEI介导的基因转移实验的体外和体内特性。(c)2002年，《科学》杂志。All rights reserved.
The delivery of a functional gene into a tissue can allow the correction of gene defaults or mutations such as those observed in severe hereditary pathologies or in cancer tissues and could lead to gene therapy. To achieve gene transfer, viral vectors are mainly used because of their intrinsic ability to enter the cells and promote expression of the transgene. However, many factors can limit the use of viral vectors, including a heavy laboratory infrastructure, and, in the case of iterative administration, the induction of immune response against viral proteins. Alternative gene transfer technologies based on nonviral vectors have been proposed. Polyethylenimine (PEI) derivatives are polycationic molecules that are able to form stable complexes with plasmidic DNA. PEI/DNA complexes attach to the cell surface, migrate into clumps that enter the cell by endocytosis and are deagregated in an acidic lysosomal compartment and/or enter the nucleus. PEI derivatives can be proposed as linear (22 kDa) or reticulated (25 kDa) molecules that prove efficient for gene transfer in vitro and in vivo. Besides extensive applications of unsubstituted PEI, glycosylated-PEI derivatives were proposed and reported to enhance gene transfer efficiency through decreased size and aggregation of PEI/DNA complexes. Galactosylated-PEI derivatives have been reported to enhance interactions with cell membranes through carbohydrate-binding protein recognition and specifically target PEI/DNA complexes toward biological systems that express galectins. More recently, glucosylated PEI derivatives have been shown to yield higher and longer-lasting transgene expression than unsubstituted-PEI in human head and neck carcinoma tumor cells. In the present paper, a review of in vitro and in vivo properties of PEI-mediated gene transfer experiments is presented. (c) 2002 Prous Science. All rights reserved.