Designing Biological Circuits: From Principles to Applications

Chakraborty, Debomita; Rengaswamy, Raghunathan; Raman, Karthik

doi:10.1021/acssynbio.1c00557

Cited by 12 publications

(8 citation statements)

References 68 publications

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“…Wroblewska et al [75] used RBPs to function as both the input and the output of RNA regulatory devices in post-transcriptional circuits, thus making it possible to design circuits that would have control over cellular behavior without genetic modifications. Numerous reports have further reviewed these biological parts and their functions within a given circuit [76][77][78][79][80][81][82][83].…”

Section: Design Of Genetic Circuitsmentioning

confidence: 99%

A Genetic Circuit Design for Targeted Viral RNA Degradation

Bello,

Popoola,

Okpuzor

et al. 2023

Bioengineering

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Advances in synthetic biology have led to the design of biological parts that can be assembled in different ways to perform specific functions. For example, genetic circuits can be designed to execute specific therapeutic functions, including gene therapy or targeted detection and the destruction of invading viruses. Viral infections are difficult to manage through drug treatment. Due to their high mutation rates and their ability to hijack the host’s ribosomes to make viral proteins, very few therapeutic options are available. One approach to addressing this problem is to disrupt the process of converting viral RNA into proteins, thereby disrupting the mechanism for assembling new viral particles that could infect other cells. This can be done by ensuring precise control over the abundance of viral RNA (vRNA) inside host cells by designing biological circuits to target vRNA for degradation. RNA-binding proteins (RBPs) have become important biological devices in regulating RNA processing. Incorporating naturally upregulated RBPs into a gene circuit could be advantageous because such a circuit could mimic the natural pathway for RNA degradation. This review highlights the process of viral RNA degradation and different approaches to designing genetic circuits. We also provide a customizable template for designing genetic circuits that utilize RBPs as transcription activators for viral RNA degradation, with the overall goal of taking advantage of the natural functions of RBPs in host cells to activate targeted viral RNA degradation.

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Section: Design Of Genetic Circuitsmentioning

confidence: 99%

A Genetic Circuit Design for Targeted Viral RNA Degradation

Bello,

Popoola,

Okpuzor

et al. 2023

Bioengineering

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“…Construction of artificial signaling pathways (ASPs) to reprogram the communications of the genetic networks is a long‐term task for cell engineering [1–4] . Many types of synthetic circuits have been generated to control the signal transduction and regulate specific gene expression [5–10] . Ideally, any change of one gene expression may be sensed as a signal to regulate the performance of another gene through synthetic circuits.…”

Section: Introductionmentioning

confidence: 99%

Harnessing Catalytic RNA Circuits for Construction of Artificial Signaling Pathways in Mammalian Cells

Wu,

Zhang

et al. 2024

Angewandte Chemie

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Engineering of genetic networks with artificial signaling pathways (ASPs) can reprogram cellular responses and phenotypes under different circumstances for a variety of diagnostic and therapeutic purposes. However, construction of ASPs between originally independent endogenous genes in mammalian cells is highly challenging. Here we report an amplifiable RNA circuit that can theoretically build regulatory connections between any endogenous genes in mammalian cells. We harness the system of catalytic hairpin assembly with combination of controllable CRISPR‐Cas9 function to transduce the signals from distinct messenger RNA expression of trigger genes into manipulation of target genes. Through introduction of these RNA‐based genetic circuits, mammalian cells are endowed with autonomous capabilities to sense the changes of RNA expression either induced by ligand stimuli or from various cell types and control the cellular responses and fates via apoptosis‐related ASPs. Our design provides a generalized platform for construction of ASPs inside the genetic networks of mammalian cells based on differentiated RNA expression.

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“…An implicit, iterative Design–Build–Test–Learn (DBTL) process is often used to develop these ingenious genetic circuits. − However, bias is introduced into the DBTL process in almost all of its steps, and the variability of environmental factors that affect a circuit’s behavior is often not considered. For example, fluorescence proteins are used as reporter genes.…”

Section: Introductionmentioning

confidence: 99%

Investigating and Modeling the Factors That Affect Genetic Circuit Performance

Zilberzwige-Tal,

Fontanarrosa,

Bychenko

et al. 2023

ACS Synth. Biol.

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Over the past 2 decades, synthetic biology has yielded ever more complex genetic circuits that are able to perform sophisticated functions in response to specific signals. Yet, genetic circuits are not immediately transferable to an outside-the-lab setting where their performance is highly compromised. We propose introducing a broader test step to the design−build−test− learn workflow to include factors that might contribute to unexpected genetic circuit performance. As a proof of concept, we have designed and evaluated a genetic circuit in various temperatures, inducer concentrations, nonsterilized soil exposure, and bacterial growth stages. We determined that the circuit's performance is dramatically altered when these factors differ from the optimal lab conditions. We observed significant changes in the time for signal detection as well as signal intensity when the genetic circuit was tested under nonoptimal lab conditions. As a learning effort, we then proceeded to generate model predictions in untested conditions, which is currently lacking in synthetic biology application design. Furthermore, broader test and learn steps uncovered a negative correlation between the time it takes for a gate to turn ON and the bacterial growth phases. As the synthetic biology discipline transitions from proof-of-concept genetic programs to appropriate and safe application implementations, more emphasis on test and learn steps (i.e., characterizing parts and circuits for a broad range of conditions) will provide missing insights on genetic circuit behavior outside the lab.

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Designing Biological Circuits: From Principles to Applications

Cited by 12 publications

References 68 publications

A Genetic Circuit Design for Targeted Viral RNA Degradation

A Genetic Circuit Design for Targeted Viral RNA Degradation

Harnessing Catalytic RNA Circuits for Construction of Artificial Signaling Pathways in Mammalian Cells

Investigating and Modeling the Factors That Affect Genetic Circuit Performance

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