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. Author manuscript; available in PMC: 2010 Feb 22.
Published in final edited form as: Mol Ther. 2007 Apr 24;15(6):1053–1064. doi: 10.1038/sj.mt.6300181

Figure 1. Transcription amplification targeting systems.

Figure 1

(a) The two-step transcriptional amplification (TSTA) system consists of a two-step transcriptional activation process. In the first step, the artificial GAL4-VP16 activator is expressed in a tissue-specific manner by virtue of regulation by a tissue- or cancer-specific promoter (e.g., prostate-specific antigen promoter). In the second step, the GAL4-VP16 protein binds to five GAL4 DNA binding sites upstream of a minimal promoter, and activates expression of a reporter gene or a therapeutic gene. (b) A new amplification system, a novel positive feedback loop with prostate specificity (PFLPS).45 Both tet-transactivator (tTA) and green fluorescent protein (GFP) genes are expressed in a tissue-specific manner by ARR2PB promoters. Binding of tTA protein to the tet-responsive element (TRE) sequences upstream of the ARR2PB promoters can induce GFP and tTA expression further, initiating a positive feedback loop. In non-prostate cells, where the ARR2PB promoter is inactive, gene expression would not be induced. (c) Cre-lox system-mediated activation of gene expression. Cre recombinase expression is regulated by a tissue- or cancer-specific promoter. Activation of transgene expression is induced by removal of the translational inhibition sequence by a Cre-specific recombination between the two loxP sites.