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1 May 2006 Photochemical Internalization of Transgenes Controlled by the Heat-shock Protein 70 Promoter
Lina Prasmickaite, Marit Hellum, Olav Kaalhus, Anders Høgset, Ernst Wagner, Kristian Berg
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Abstract

Photochemical internalization (PCI) is a targeting technique that facilitates endosomal escape of macromolecules, such as transgenes, in response to photochemical treatment with endosome/lysosome-localized photosensitizers, such as disulfonated meso-tetraphenylporphine (TPPS2a). In gene therapy this leads to enhanced transgene expression. Moreover, photochemical treatment generally activates transcription of stress-response genes, such as heat-shock proteins (HSPs), via stimulation of corresponding promoters. Therefore, we used HSP70 (HSPp; a promoter from the HSP family gene) and investigated whether the PCI stimulus could also activate HSPp and thereby stimulate transcription (expression) of the HSPp-controlled transgene internalized via PCI. Using human colorectal carcinoma and hepatoma cell lines in vitro, we showed that TPPS2a-based photochemical treatment enhances expression of cellular HSP70, which correlated with a photochemically enhanced expression (approximately 2-fold, at PCI-optimal doses) of the HSPp-controlled transgene integrated in the genome. Furthermore, PCI enhanced expression of the HSPp-controlled episomal transgene delivered as a plasmid. However, in plasmid-based transfection, PCI-mediated enhancement with HSPp did not exceed the enhancement achieved with the constitutive active CMV promoter. In conclusion, we demonstrated that the PCI-relevant treatment initiates HSP70 response and that the HSP70 promoter can be used in combination with PCI, leading to PCI-enhanced expression of the HSPp-controlled transgene.

Lina Prasmickaite, Marit Hellum, Olav Kaalhus, Anders Høgset, Ernst Wagner, and Kristian Berg "Photochemical Internalization of Transgenes Controlled by the Heat-shock Protein 70 Promoter," Photochemistry and Photobiology 82(3), 809-816, (1 May 2006). https://doi.org/10.1562/2005-11-07-RA-731
Received: 7 November 2005; Accepted: 1 January 2006; Published: 1 May 2006
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