Photochemical transfection: a technology for efficient light-directed gene delivery.

Anders Høgset, Lina Prasmickaite, Marit Hellum, Birgit O Engesaeter, Vibeke M Olsen, Torunn E Tjelle, Carl J Wheeler, Kristian Berg
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引用次数: 36

Abstract

Most synthetic gene delivery vectors are taken up in the cell by endocytosis, and inefficient escape of the transgene from endocytic vesicles often is a major barrier for gene transfer by such vectors. To improve endosomal release we have developed a new technology, named photochemical internalization (PCI). PCI is based on photochemical reactions initiated by photosensitizing compounds localized in endocytic vesicles, inducing rupture of these vesicles upon light exposure. PCI constitutes an efficient light-inducible gene transfer method in vitro, which potentially can be developed into a site-specific method for gene delivery in in vivo gene therapy. In this paper the principle behind the PCI technology and the effect of PCI on transfection with different synthetic gene delivery vectors are reviewed. PCI treatment by the photosensitizer aluminum phthalocyanine (AlPcS2a) strongly improves transfection mediated by cationic polymers (e.g., poly-L-lysine and polyethylenimine), while the effect on transfection with cationic lipids is more variable. The timing of the light treatment relative to the transfection period was also important, indicating that release of the DNA from early endosomes is important for the outcome of PCI-induced transfection. The possibilities of using PCI as a technology for efficient, site-specific gene delivery in in vivo gene therapy is discussed.

光化学转染:一种高效的光导基因传递技术。
大多数合成的基因传递载体在细胞内通过内吞作用被吸收,转基因从内吞囊泡的低效逃逸往往是这些载体转移基因的主要障碍。为了改善内体释放,我们开发了光化学内化(PCI)技术。PCI是基于光化学反应,由定位于内吞囊泡中的光敏化合物引发,在光照射下诱导这些囊泡破裂。PCI在体外是一种高效的光诱导基因转移方法,有可能发展成为体内基因治疗中基因传递的位点特异性方法。本文综述了PCI技术的原理及其对不同合成基因载体转染的影响。采用光敏剂酞菁铝(AlPcS2a)治疗PCI,可显著改善阳离子聚合物(如聚l -赖氨酸和聚乙烯亚胺)介导的转染,而对阳离子脂质转染的影响则更为多变。相对于转染周期的光处理时间也很重要,这表明DNA从早期内体释放对pci诱导转染的结果很重要。讨论了在体内基因治疗中使用PCI作为一种高效、位点特异性基因传递技术的可能性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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