Streptomyces-derived quorum-sensing systems engineered for adjustable transgene expression in mammalian cells and mice.

@article{citeulike:187, abstract = {Prokaryotic transcriptional regulatory elements have been adopted for controlled expression of cloned genes in mammalian cells and animals, the cornerstone for gene-function correlations, drug discovery, biopharmaceutical manufacturing as well as advanced gene therapy and tissue engineering. Many prokaryotes have evolved specific molecular communication systems known as quorum-sensing to coordinate population-wide responses to physiological and/or physicochemical signals. A generic bacterial quorum-sensing system is based on a diffusible signal molecule that prevents binding of a repressor to corresponding operator sites thus resulting in derepression of a target regulon. In Streptomyces, a family of butyrolactones and their corresponding receptor proteins, serve as quorum-sensing systems that control morphological development and antibiotic biosynthesis. Fusion of the Streptomyces coelicolor quorum-sensing receptor (ScbR) to a eukaryotic transactivation domain (VP16) created a mammalian transactivator (SCA) which binds and adjusts transcription from chimeric promoters containing an SCA-specific operator module (P(SPA)). Expression of erythropoietin or the human secreted alkaline phosphatase (SEAP) by this quorum-sensor-regulated gene expression system (QuoRex) could be fine-tuned by non-toxic butyrolactones in a variety of mammalian cells including human primary and mouse embryonic stem cells. Following intraperitoneal implantation of microencapsulated Chinese hamster ovary cells transgenic for QuoRex-controlled SEAP expression into mice, the serum levels of this model glycoprotein could be adjusted to desired concentrations using different butyrolactone dosing regimes.}, address = {Institute of Biotechnology, Swiss Federal Institute of Technology, ETH Hoenggerberg, CH-8093 Zurich, Switzerland.}, author = {Weber, W. and Schoenmakers, R. and Spielmann, M. and El-Baba, M. D. and Folcher, M. and Keller, B. and Weber, C. C. and Link, N. and van de Wetering, P. and Heinzen, C. and Jolivet, B. and S\'{e}quin, U. and Aubel, D. and Thompson, C. J. and Fussenegger, M. }, citeulike-article-id = {187}, issn = {1362-4962}, journal = {Nucleic Acids Res}, keywords = {inducible-expression, project, quorum}, month = {July}, number = {14}, posted-at = {2004-11-11 10:32:15}, title = {Streptomyces-derived quorum-sensing systems engineered for adjustable transgene expression in mammalian cells and mice.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/12853648}, volume = {31}, year = {2003} }

TY - JOUR ID - citeulike:187 L3 - citeulike-article-id:187 TI - Streptomyces-derived quorum-sensing systems engineered for adjustable transgene expression in mammalian cells and mice. JF - Nucleic Acids Res VL - 31 IS - 14 AD - Institute of Biotechnology, Swiss Federal Institute of Technology, ETH Hoenggerberg, CH-8093 Zurich, Switzerland. SN - 1362-4962 N2 - Prokaryotic transcriptional regulatory elements have been adopted for controlled expression of cloned genes in mammalian cells and animals, the cornerstone for gene-function correlations, drug discovery, biopharmaceutical manufacturing as well as advanced gene therapy and tissue engineering. Many prokaryotes have evolved specific molecular communication systems known as quorum-sensing to coordinate population-wide responses to physiological and/or physicochemical signals. A generic bacterial quorum-sensing system is based on a diffusible signal molecule that prevents binding of a repressor to corresponding operator sites thus resulting in derepression of a target regulon. In Streptomyces, a family of butyrolactones and their corresponding receptor proteins, serve as quorum-sensing systems that control morphological development and antibiotic biosynthesis. Fusion of the Streptomyces coelicolor quorum-sensing receptor (ScbR) to a eukaryotic transactivation domain (VP16) created a mammalian transactivator (SCA) which binds and adjusts transcription from chimeric promoters containing an SCA-specific operator module (P(SPA)). Expression of erythropoietin or the human secreted alkaline phosphatase (SEAP) by this quorum-sensor-regulated gene expression system (QuoRex) could be fine-tuned by non-toxic butyrolactones in a variety of mammalian cells including human primary and mouse embryonic stem cells. Following intraperitoneal implantation of microencapsulated Chinese hamster ovary cells transgenic for QuoRex-controlled SEAP expression into mice, the serum levels of this model glycoprotein could be adjusted to desired concentrations using different butyrolactone dosing regimes. KW - inducible-expression KW - project KW - quorum AU - Weber, W AU - Schoenmakers, R AU - Spielmann, M AU - El-Baba, MD AU - Folcher, M AU - Keller, B AU - Weber, CC AU - Link, N AU - van de Wetering, P AU - Heinzen, C AU - Jolivet, B AU - Séquin, U AU - Aubel, D AU - Thompson, CJ AU - Fussenegger, M PY - 2003/07/15/ UR - http://view.ncbi.nlm.nih.gov/pubmed/12853648 ER -