Gene delivery with biocompatible cationic polymer: Pharmacogenomic analysis on cell bioactivity
Gene delivery with biocompatible cationic polymer: Pharmacogenomic analysis on cell bioactivity
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DOI：
10.1016/j.biomaterials.2007.07.019
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发表时间：
2007-12-01
期刊：
影响因子：
14
通讯作者：
Kataoka, Kazunori
中科院分区：
文献类型：
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作者：
Masago, Kayo;Itaka, Keiji;Kataoka, Kazunori
非病毒基因传递系统的可用性取决于它们在基因导入过程中的能力和安全性。本研究从生物分子机制的角度对复合制剂的安全性问题进行了分析。以N-(2-氨基乙基)氨基乙基为侧链的新型聚合物P[Asp(Det)]与传统的线型聚乙二胺(LPEI)进行了比较。将P[Asp(Det)]转入生物发光细胞系后，保持了荧光素酶的稳定表达。相反，LPEI抑制了荧光素酶的表达，而外源报告基因的表达与LPEI相似。对看家基因表达和PDNA摄取的评估表明，LPEI具有时间依赖性的毒性，扰乱了细胞的动态平衡。一直以来，功能基因导入诱导成骨分化只通过P[Asp(Det)]实现，尽管LPEI获得了明显的基因表达。考虑到这一方面的安全性是至关重要的，特别是当基因导入应用于原代细胞以调节细胞分化等功能时。这种着眼于细胞动态平衡的生物分子分析有利于评估基因递送系统在临床上的实用性。(C)2007爱思唯尔有限公司。保留所有权利。
The availability of non-viral gene delivery systems is determined by their capacity and safety during gene introduction. In this study, the safety issues of polyplex were analyzed from the standpoint of the biomolecular mechanisms. P[Asp(DET)], a newly developed polymer, polyasparagine carrying the N-(2-aminoethyl)aminoethyl group as the side chain which was recently revealed to show good transfection efficiency to primary cells, was compared to conventional linear poly(ethylenimine) (LPEI). After transfection toward a bioluminescent cell line, P[Asp(DET)] maintained the expression level of stably expressing luciferase. In contrast, LPEI showed a decrease in the luciferase expression, while the similar expression of exogenous reporter gene was obtained. Evaluation of the housekeeping genes expression as well as the profiles of pDNA uptake after transfection suggested the time-dependent toxicity of LPEI that perturbs cellular homeostasis. Consistently, the induction of osteogenic differentiation by functional gene introduction was achieved only by P[Asp(DET)], even though appreciable expression of the gene was achieved by LPEI. It is crucial that this aspect of safety be taken into account, especially when the gene introduction is applied to primary cells to regulate such cell function as differentiation. This biomolecular analysis focusing on cellular homeostasis is beneficial for assessing the practicability of the gene delivery systems for clinical application. (C) 2007 Elsevier Ltd. All rights reserved.