title: Engineered Streptomyces quorum-sensing components enable inducible siRNA-mediated translation control in mammalian cells and adjustable transcription control in mice.
abstract: BACKGROUND
  Recent advances in functional genomics, gene therapy, tissue engineering, drug discovery and biopharmaceuticals production have been fostered by precise small-molecule-mediated fine-tuning of desired transgenes.
  
  
  METHODS
  Capitalizing on well-evolved quorum-sensing regulatory networks in Streptomyces coelicolor we have designed a mammalian regulation system inducible by the non-toxic butyrolactone SCB1. Fusion of the S. coelicolor SCB1 quorum-sensing receptor ScbR to the human Kox-1-derived transsilencing domain reconstituted a mammalian transsilencer (SCS) able to repress transcription from SCS-specific operator-containing promoters in a reverse SCB1-adjustable manner.
  
  
  RESULTS
  This quorum-sensing-derived mammalian transgene control system (Q-ON) enabled precise SCB1-specific fine-tuning of (i) desired transgene transcription in a variety of mammalian/human cell lines and human primary cells, (ii) small interfering RNA-mediated posttranscriptional knockdown (siRNA) in mammalian cells, and (iii) dosing of a human glycoprotein in mice.
  
  
  CONCLUSIONS
  As exemplified by Q-ON technology, bacterial quorum-sensing regulons may represent a near-infinite source for the design of mammalian gene control systems compatible with molecular interventions relevant to future gene therapy and tissue engineering scenarios.
authors.affiliation: Institute of Biotechnology, Swiss Federal Institute of Technology, ETH Zurich, ETH Hoenggerberg, CH-8093 Zurich, Switzerland.
authors.forename: Wilfried
authors.initials: W
authors.lastname: Weber
authors.forename: Laetitia
authors.initials: L
authors.lastname: Malphettes
authors.forename: Maria
authors.initials: M
authors.lastname: de Jesus
authors.forename: Ronald
authors.initials: R
authors.lastname: Schoenmakers
authors.forename: Marie Daoud
authors.initials: MD
authors.lastname: El-Baba
authors.forename: Manuela
authors.initials: M
authors.lastname: Spielmann
authors.forename: Bettina
authors.initials: B
authors.lastname: Keller
authors.forename: Cornelia C
authors.initials: CC
authors.lastname: Weber
authors.forename: Petra
authors.initials: P
authors.lastname: van de Wetering
authors.forename: Dominique
authors.initials: D
authors.lastname: Aubel
authors.forename: Florian M
authors.initials: FM
authors.lastname: Wurm
authors.forename: Martin
authors.initials: M
authors.lastname: Fussenegger
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D005818:Genetic Engineering; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009841:Oligonucleotides; D014176:Protein Biosynthesis / Q000502:physiology*; D034741:RNA, Small Interfering / Q000502:physiology*; D013302:Streptomyces / Q000235:genetics*; D014158:Transcription, Genetic / Q000502:physiology*; D019076:Transgenes
chemical_list: D009841:Oligonucleotides; D034741:RNA, Small Interfering; C082868:butyrolactone I; D015107:4-Butyrolactone