ArticleJournal of biological engineering2015
Synthetic feedback control using an RNAi-based gene-regulatory device.
Article in Journal of biological engineering, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 48 citations in OpenAlex.
- Engineering Cell Fate with Adaptive Feedback Control.ACS synthetic biology · 2025Article
- CRISPR perfect adaptation for robust control of cellular immune and apoptotic responses.Nucleic acids research · 2024Article
- A genetic mammalian proportional-integral feedback control circuit for robust and precise gene regulation.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Engineering synthetic RNA devices for cell control.Nature reviews. Genetics · 2022Review
- Article
- A synthetic distributed genetic multi-bit counter.iScience · 2021Article
- Context-aware synthetic biology by controller design: Engineering the mammalian cell.Cell systems · 2021Review
- Review
- Massively parallel RNA device engineering in mammalian cells with RNA-Seq.Nature communications · 2019Article
- Genetic circuits to engineer tissues with alternative functions.Journal of biological engineering · 2019Review
- Synthetic negative feedback circuits using engineered small RNAs.Nucleic acids research · 2018Article
- Synthetic control systems for high performance gene expression in mammalian cells.Nucleic acids research · 2018Article
- Bottom-up approaches in synthetic biology and biomaterials for tissue engineering applications.Journal of industrial microbiology & biotechnology · 2018Article
- System-based strategies for p53 recovery.IET systems biology · 2018Article
- Mapping the operational landscape of microRNAs in synthetic gene circuits.NPJ systems biology and applications · 2018Article
- Biomedical Applications of RNA-Based Devices.Current opinion in biomedical engineering · 2017Article
- Mammalian synthetic biology for studying the cell.The Journal of cell biology · 2017Review
- Control theory meets synthetic biology.Journal of the Royal Society, Interface · 2016Review
- Engineering dynamic cell cycle control with synthetic small molecule-responsive RNA devices.Journal of biological engineering · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHomeostasis within mammalian cells is achieved through complex molecular networks that can respond to changes within the cell or the environment and regulate the expression of the appropriate genes in response. The development of biological components that can respond to changes in the cellular environment and interface with endogenous molecules would enable more sophisticated genetic circuits and greatly advance our cellular engineering capabilities.
resultsHere we describe a platform that combines a ligand-responsive ribozyme switch and synthetic miRNA regulators to create an OFF genetic control device based on RNA interference (RNAi). We developed a mathematical model to highlight important design parameters in programming the quantitative performance of RNAi-based OFF control devices. By modifying the ribozyme switch integrated into the system, we demonstrated RNAi-based OFF control devices that respond to small molecule and protein ligands, including the oncogenic protein E2F1. We utilized the OFF control device platform to build a negative feedback control system that acts as a proportional controller and maintains target intracellular protein levels in response to increases in transcription rate.
conclusionsOur work describes a novel genetic device that increases the level of silencing from a miRNA in the presence of a ligand of interest, effectively creating an RNAi-based OFF control device. The OFF switch platform has the flexibility to be used to respond to both small molecule and protein ligands. Finally, the RNAi-based OFF switch can be used to implement a negative feedback control system, which maintains target protein levels around a set point level. The described RNAi-based OFF control device presents a powerful tool that will enable researchers to engineer homeostasis in mammalian cells.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.