Genetic manipulation of endothelial cells by viral vectors
Genetic manipulation of endothelial cells by viral vectors
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DOI：
10.1160/th09-10-0724
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发表时间：
2009-12-01
影响因子：
6.7
通讯作者：
Schnittler, Hans
中科院分区：
文献类型：
--
作者：
Lindemann, Dirk;Schnittler, Hans
在过去的几十年中，揭示内皮细胞生物学中分子机制的需求大大增加，因为越来越清楚的是，内皮细胞是几乎所有疾病和治疗（药物递送）的重要靶点，并在再生过程中发挥核心作用。在细胞生物学研究中通常用于揭示结构和功能方面的关键方法之一是通过过表达、突变变体的表达或基因沉默来调节蛋白质表达。然而，这种策略需要对相应的细胞进行遗传操作。通过化学转染技术进行的经典基因转移在各种培养细胞中效果很好，但对大多数内皮细胞类型无效。转染率和基因表达水平不足以及内皮对化学转染试剂的敏感性限制了该技术在内皮细胞生物学研究中的应用。这不仅适用于体内的原代内皮细胞培养物和内皮细胞，而且适用于内皮细胞系，例如内皮瘤细胞。最初设计用于基因治疗方法的病毒载体的发展显著改善了内皮细胞研究的方法学谱。基于逆转录病毒和腺病毒的两种病毒载体系统分别将转基因信息高效地递送到培养的内皮细胞和体内内皮细胞中。这篇综述旨在对这两种载体系统进行全面概述，这两种载体系统似乎是将基因递送到内皮细胞类型中的可靠且有效的工具。
The need for uncovering molecular mechanisms in endothelial cell biology has tremendously increased in the last decades as it became more and more clear that the endothelium is an important target in nearly all diseases and treatments (drug delivery) and plays a central role in regeneration processes. One of the critical methods generally applied in cell biology research to uncover structural and functional aspects is the modulation of protein expression by over-expression, expression of mutant variants or gene silencing. This strategy, however, requires genetic manipulation of the respective cells. The classical gene transfer by chemical transfection techniques works pretty well in a large variety of cultured cells but fails for most endothelial cell types. Insufficient transfection rates and gene expression levels as well as the sensitivity of the endothelium against chemical transfection reagents limits utilisation of this technique for endothelial cell biology research. This holds true not only for primary endothelial cell cultures and endothelial cells in vivo but also for endothelial cell lines, e.g. endothelioma cells. The development of viral vectors originally designed for gene therapy approaches has significantly improved the methodological spectrum in endothelial cell research. Two viral vector systems, based on retroviruses and adenoviruses, deliver transgenic information highly efficient into both cultured endothelial cells and in endothelial cells in vivo, respectively. This review aims to give a comprehensive overview of these two vector systems that appear to be reliable and efficient tools for gene delivery into endothelial cell types.