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Updated: Aug 21, 2026

In vivo Application of the REMOTE-control System for the Manipulation of Endogenous Gene Expression
Published on: March 29, 2019
Engineered Streptomyces quorum-sensing components enable inducible siRNA-mediated translation control in mammalian
Wilfried Weber1, Laetitia Malphettes, Maria de Jesus
1Institute of Biotechnology, Swiss Federal Institute of Technology, ETH Zurich, ETH Hoenggerberg, CH-8093 Zurich, Switzerland.
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.
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