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• W2469373669 abstract "Abstract Gene therapy has the potential to provide innovative treatments for genetic and non-genetic diseases, with the ability to auto-regulate expression levels of therapeutic molecules so that they are produced locally and in direct response to disease activity. Generating disease responsive gene therapy vectors requires knowledge of the activation profile of transcription factors (TFs) during active disease, in order to assemble binding sites for these TFs into synthetic promoters, which can be appropriately activated by the disease process. In this study, we optimised a PCR random assembly approach to generate promoters with optimal spacing between TF binding sites (TFBSs) and their distance from the TATA box. In promoters with optimal spacing, it was possible to demonstrate activation by individual transcription pathways and either additive or synergistic promoter activation when transfected cells were treated with combined stimuli. The kinetics and sensitivity of promoter activation was further explored in transduced cells and when lentivirus was directly delivered to mouse paws a synthetic promoter demonstrated excellent activation by real-time imaging in response to local inflammation." @default.
• W2469373669 created "2016-07-22" @default.
• W2469373669 creator A5026066463 @default.
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• W2469373669 creator A5077515411 @default.
• W2469373669 date "2016-07-08" @default.
• W2469373669 modified "2023-09-27" @default.
• W2469373669 title "Assembly PCR synthesis of optimally designed, compact, multi-responsive promoters suited to gene therapy application" @default.
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• W2469373669 doi "https://doi.org/10.1038/srep29388" @default.
• W2469373669 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4937410" @default.
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• W2469373669 hasPublicationYear "2016" @default.
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