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An Ecdysone Receptor-based Singular Gene Switch for Deliberate Expression of Transgene with Robustness, Reversibility, and Negligible Leakiness
Published on: May 7, 2018
DOCTER: a genetically encoded switchable protein module for ERα-mediated transcriptional regulation
Jinmin Wang1, Jingfang Liu1, Dandan Peng2
1Department of Biomedical Engineering, MOE Key Laboratory of Biomedical Engineering, Zhejiang Provincial Key Laboratory of Intelligent Sensing and Advanced Medical Instrument, Zhejiang University, Hangzhou, China.
Gene Therapy
|May 26, 2026
Summary
Researchers developed DOCTER, a novel system for reversible control of estrogen receptor alpha (ERα) activity. This drug-inducible system precisely switches ERα-mediated gene transcription on and off, offering new therapeutic and research possibilities.
Area of Science:
- Molecular Biology
- Genetics
- Cancer Therapeutics
Background:
- Estrogen receptor (ER)-mediated signaling is crucial in ER-positive cancers.
- Targeting ER signaling is a key therapeutic strategy.
- Existing methods lack precise temporal control.
Purpose of the Study:
- To develop a switchable system for ERα-mediated transcriptional regulation.
- To enable precise, reversible on/off control of ERα activity.
- To explore applications in breast cancer therapy and genetic research.
Main Methods:
- Development of the DOCTER (Drug-induced On-Off Competitor for Transcription mediated by ERα) system.
- Integration of the Tet-On Cre-loxP recombination system for reversible switching.
- Utilized a multi-color fluorescent reporting system for real-time monitoring.
Main Results:
- DOCTER effectively inhibits ERα-mediated transcription in breast cancer cells.
- Modulation of both exogenous and endogenous gene expression was achieved.
- The system remains effective in cells with ERα ligand-binding domain (LBD) mutations.
- Controllable and reversible inhibition was demonstrated upon drug induction.
- Real-time visualization of DOCTER switch-off within 24 hours was achieved.
Conclusions:
- DOCTER provides a novel approach for time-specific transcriptional regulation.
- The system offers precise and reversible control over ERα activity.
- This technology has broad potential for genetic research and therapeutic development.
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