Recombinant Expression System for Robust Cellular Network Control

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Solution Overview

Problem

Existing artificial genetic circuits lack robustness in controlling cellular networks, particularly when tight regulation of setpoints is required, making them susceptible to environmental fluctuations.

Innovation Solution

A recombinant expression system is introduced, comprising nucleic acids encoding a controller molecule that regulates an actuator molecule, which in turn controls an output molecule, with feedback mechanisms and anti-controller molecules to maintain stability and adjust to perturbations, implementing proportional, integral, and derivative control mechanisms.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If artificial genetic circuits are used to control cellular networks, then the ability to manipulate and control gene regulatory networks is improved, but robustness towards environmental fluctuations deteriorates

Engineering Contradiction:
Improveability to manipulate and control gene regulatory networksVSAvoidrobustness towards environmental fluctuations
Core Design Contradiction:
Ease of operationVSReliability

Solution Approach 1:

The patent implements feedback mechanisms by introducing controller molecules that sense output molecule concentrations and adjust actuator molecule expression accordingly. The system includes feedback loops where controller molecules regulate actuator molecules, which in turn regulate output molecules, creating a closed-loop control system that maintains stability despite environmental changes.

Inventive Principle:
Principle #23Feedback

Solution Approach 2:

The patent introduces controller molecules as intermediary elements between actuator molecules and output molecules. These controller molecules act as mediators that process information about output concentrations and translate them into appropriate actuator regulation, adding a layer of control that improves robustness while maintaining操纵ability.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Manufacturing precision

If tight regulation of setpoint is implemented, then control precision is improved, but susceptibility to environmental fluctuations increases

Engineering Contradiction:
Improvetight regulation of setpointVSAvoidsusceptibility to environmental fluctuations
Core Design Contradiction:
Manufacturing precisionVSObject-affected harmful factors

Solution Approach 1:

The patent employs compensatory mechanisms that anticipate and counteract environmental fluctuations before they significantly impact the setpoint. The controller molecules are designed to detect early deviations and initiate corrective actions, cushioning the system against the full force of environmental disturbances and maintaining tight regulation.

Inventive Principle:
Principle #11Beforehand cushioning (Prior cushioning)

Solution Approach 2:

The patent utilizes parameter changes in the controller molecules' regulatory characteristics to adapt to environmental conditions. By dynamically adjusting regulation parameters such as binding affinities and expression levels, the system maintains precise setpoint control while becoming less susceptible to environmental fluctuations.

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentUS20240018540A1Expression system and method for controlling a network in a cell and cell comprising the expression system
Publication Date: 2024.01.18 ETH ZURICH
  • US20240018540A1 patent drawing
  • US20240018540A1 patent drawing
  • US20240018540A1 patent drawing

AI summary

The invention relates to an expression system for controlling a network in a cell, wherein the network comprises an actuator molecule and an output molecule, wherein the output molecule is positively or negatively regulated by the actuator molecule, wherein the expression system comprises a recombinant gene encoding a first controller molecule, wherein the first controller molecule positively or negatively regulates the actuator molecule. The invention further relates to a cell comprising the expression system, to a cell for use as a medicament and to a method for controlling a network in a cell.