Non-viral gene delivery regulated by stiffness of cell adhesion substrates
Non-viral gene delivery regulated by stiffness of cell adhesion substrates
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DOI：
10.1038/nmat1392
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发表时间：
2005-06-01
期刊：
影响因子：
41.2
通讯作者：
Mooney, DJ
中科院分区：
文献类型：
--
作者：
Kong, HJ;Liu, JD;Mooney, DJ
由于病毒载体的安全性问题(4)，非病毒基因载体通常用于基因治疗(1-3)。然而，非病毒载体受到基因转染和细胞表达水平低的困扰(1,2)。目前提高非病毒基因传递效率的努力主要集中在传递载体的操作上(5-12)，而细胞环境对DNA摄取的影响常常被忽视。已发现细胞粘附基质的机械特性（例如刚性）可介导细胞功能的许多方面，包括增殖、迁移和分化 (13-17)，这表明粘附基质的力学特性可能调节细胞摄取外源信号分子的能力。在本报告中，我们提出了细胞粘附基质的刚性对基因转移和表达水平的关键作用。该机制与细胞增殖的物质控制有关，并使用荧光共振能量转移 (FRET) 技术进行了研究 (18-21)。这项研究为非病毒基因治疗提供了一种新的基于材料的控制点。
Non-viral gene vectors are commonly used for gene therapy(1-3) owing to safety concerns with viral vectors(4). However, nonviral vectors are plagued by low levels of gene transfection and cellular expression(1,2). Current efforts to improve the efficiency of non-viral gene delivery are focused on manipulations of the delivery vector(5-12), whereas the influence of the cellular environment in DNA uptake is oft en ignored. The mechanical properties ( for example, rigidity) of the substrate to which a cell adheres have been found to mediate many aspects of cell function including proliferation, migration and differentiation(13-17), and this suggests that the mechanics of the adhesion substrate may regulate a cell's ability to uptake exogeneous signalling molecules. In this report, we present a critical role for the rigidity of the cell adhesion substrate on the level of gene transfer and expression. The mechanism relates to material control over cell proliferation, and was investigated using a fluorescent resonance energy transfer (FRET) technique(18-21). This study provides a new material-based control point for non-viral gene therapy.