ArticleNature communications2020
Characterization and mitigation of gene expression burden in mammalian cells.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
What it found
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Who cites it
89 citing papers in PubMed, 163 citations in OpenAlex.
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- Systematic Evaluation of Different Ribonucleoprotein Complexes as Posttranscriptional Biosensors in Cell-Free TX-TL Systems.ACS synthetic biology · 2026Article
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- GCAD: A Computational Framework for Mammalian Genetic Program Computer-Aided Design.ACS synthetic biology · 2026Article
- Resource Competition and Growth Dilution Modulate Synthetic Gene Cascade Dynamics.ACS synthetic biology · 2026Article
- Harnessing CRISPRi Competition to Develop Multimodule Controllers for Resource-Aware Circuit Design.Methods in molecular biology (Clifton, N.J.) · 2026Article
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- Integrating synthetic biology to understand and engineer the heart, lung, blood, and sleep systems.Cell systems · 2025Review
- Mammalian synthetic gene circuits for biopharmaceutical development & manufacture.NPJ systems biology and applications · 2025Review
- How cells tame noise while maintaining ultrasensitive transcriptional responses.PLoS computational biology · 2025Article
- AI-directed gene fusing prolongs the evolutionary half-life of synthetic gene circuits.Science advances · 2025Article
- CRISPRi-Linked Multimodule Negative Feedback Loops to Address Winner-Take-All Resource Competition.ACS synthetic biology · 2025Article
- GCAD: a Computational Framework for Mammalian Genetic Program Computer-Aided Design.bioRxiv : the preprint server for biology · 2025Article
- The advantage of periodic over constant signalling in microRNA-mediated regulation.Nucleic acids research · 2025Article
- An inducible tethered function assay reveals differential regulatory effects for the RNA-binding protein YBX3 and its domains.bioRxiv : the preprint server for biology · 2025Article
- Why cellular computations challenge our design principles.Seminars in cell & developmental biology · 2025Review
- Model-guided design of microRNA-based gene circuits supports precise dosage of transgenic cargoes into diverse primary cells.Cell systems · 2025Article
- CRISPRi-Linked Multi-Module Negative Feedback Loops to Address Winner-Take-All Resource Competition.bioRxiv : the preprint server for biology · 2025Article
- Multi-Layer Autocatalytic Feedback Enables Integral Control Amidst Resource Competition and Across Scales.ACS synthetic biology · 2025Article
29 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite recent advances in circuit engineering, the design of genetic networks in mammalian cells is still painstakingly slow and fraught with inexplicable failures. Here, we demonstrate that transiently expressed genes in mammalian cells compete for limited transcriptional and translational resources. This competition results in the coupling of otherwise independent exogenous and endogenous genes, creating a divergence between intended and actual function. Guided by a resource-aware mathematical model, we identify and engineer natural and synthetic miRNA-based incoherent feedforward loop (iFFL) circuits that mitigate gene expression burden. The implementation of these circuits features the use of endogenous miRNAs as elementary components of the engineered iFFL device, a versatile hybrid design that allows burden mitigation to be achieved across different cell-lines with minimal resource requirements. This study establishes the foundations for context-aware prediction and improvement of in vivo synthetic circuit performance, paving the way towards more rational synthetic construct design in mammalian cells.
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Registered trials
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.