کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4305130 1288525 2007 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Systemic and Localized Reversible Regulation of Transgene Expression by Tetracycline with tetR-Mediated Transcription Repression Switch
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی عمل جراحی
پیش نمایش صفحه اول مقاله
Systemic and Localized Reversible Regulation of Transgene Expression by Tetracycline with tetR-Mediated Transcription Repression Switch
چکیده انگلیسی

BackgroundWe recently developed a new tetracycline-inducible gene switch employing the tetracycline operator-containing hCMV major immediate-early promoter and the tetracycline repressor, tetR, rather than the previously used tetR-mammalian cell transcription factor fusion derivatives.Materials and methodsThe present study demonstrates that this tetR-mediated transcription repression system can function as a powerful gene switch for On-and-Off regulation of therapeutic gene expression in ex vivo gene transfer protocols. Firstly, for achieving regulated gene expression in a localized tissue environment, R11/OEGF cells, a stable line that expresses hEGF under the control of the tetR-mediated transcription repression switch, were transplanted into porcine full-thickness wounds enclosed by wound chambers.ResultsBy topically applying tetracycline in wound chambers at various concentrations or at different time points post-transplantation, the levels and timing of hEGF expression in transplanted wounds could be reversibly regulated by tetracycline. Over 3000-fold induction in hEGF expression was achieved in the local wound microenvironment. Secondly, R11/OEGF cells were intramuscularly injected into NCr outbread nude mice to test the efficacy of intermittent systemic gene delivery of a soluble peptide(s).ConclusionsBasal circulating hEGF was undetectable and induced up to at least 1,500-fold after administration of tetracycline. Furthermore, the timing and duration of hEGF expression could be finely adjusted by the presence or the absence of tetracycline in the drinking water.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Surgical Research - Volume 138, Issue 2, April 2007, Pages 267–274
نویسندگان
, , , , , , , ,