Høgset Anders, Prasmickaite Lina, Hellum Marit, Engesaeter Birgit O, Olsen Vibeke M, Tjelle Torunn E, Wheeler Carl J, Berg Kristian
PCI Biotech AS, Hoffsvn, 48, N-0377 Oslo, Norway.
Somat Cell Mol Genet. 2002 Nov;27(1-6):97-113. doi: 10.1023/a:1022979806314.
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.
大多数合成基因递送载体通过内吞作用进入细胞，而转基因从内吞小泡中低效逃逸通常是此类载体进行基因转移的主要障碍。为了改善内体释放，我们开发了一种名为光化学内化（PCI）的新技术。PCI基于内吞小泡中定位的光敏化合物引发的光化学反应，光照时诱导这些小泡破裂。PCI在体外构成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一种位点特异性的基因递送方法。本文综述了PCI技术背后的原理以及PCI对不同合成基因递送载体转染的影响。用光敏剂铝酞菁（AlPcS2a）进行PCI处理可显著提高阳离子聚合物（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具变数。相对于转染期的光照处理时间也很重要，这表明从早期内体释放DNA对PCI诱导转染的结果很重要。还讨论了将PCI用作体内基因治疗中高效、位点特异性基因递送技术的可能性。
