Context-dependent redesign of robust synthetic gene circuits.

Unavoidable circuit–host interactions confound the modularity of engineered synthetic gene circuits. Unintuitive emergent dynamics can be better understood by incorporating the influence of feedback context factors into the system. Mechanistic understanding of the intricate relationships between circuits and hosts enhances our ability to predict and control them. Complementary control strategies can be incorporated into circuit design to mitigate unwanted effects. Early identification of context-dependent modes of failure can accelerate circuit development. Cells provide dynamic platforms for executing exogenous genetic programs in synthetic biology, resulting in highly context-dependent circuit performance. Recent years have seen an increasing interest in understanding the intricacies of circuit–host relationships, their influence on the synthetic bioengineering workflow, and in devising strategies to alleviate undesired effects. We provide an overview of how emerging circuit–host interactions, such as growth feedback and resource competition, impact both deterministic and stochastic circuit behaviors. We also emphasize control strategies for mitigating these unwanted effects. This review summarizes the latest advances and the current state of host-aware and resource-aware design of synthetic gene circuits. Cells provide dynamic platforms for executing exogenous genetic programs in synthetic biology, resulting in highly context-dependent circuit performance. Recent years have seen an increasing interest in understanding the intricacies of circuit–host relationships, their influence on the synthetic bioengineering workflow, and in devising strategies to alleviate undesired effects. We provide an overview of how emerging circuit–host interactions, such as growth feedback and resource competition, impact on both deterministic and stochastic circuit behaviors. We also emphasize control strategies for mitigating these unwanted effects. This review summarizes the latest advances and the current state of host-aware and resource-aware design of synthetic gene circuits. [ABSTRACT FROM AUTHOR]