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Characterization and mitigation of gene expression burden in mammalian cells

Frei, Timothy; Cella, Federica; Tedeschi, Fabiana; Gutiérrez, Joaquín; Stan, Guy-Bart; Khammash, Mustafa; Siciliano, Velia;
Open Access
Abstract
<p><strong>Abstract</strong></p> <p>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 ex...
Persistent Identifiers
Funded by
EC| COSY-BIO
Project
COSY-BIO
Control Engineering of Biological Systems for Reliable Synthetic Biology Applications
  • Funder: European Commission (EC)
  • Project Code: 766840
  • Funding stream: H2020
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