Molecular Feedback Circuits for Self-Regulating Cellular Output
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Solution Overview
Problem
Current engineered cells require continuous external input to modulate their output, lacking self-regulation mechanisms to maintain desired levels of cellular activity over time, which is inefficient and impractical for long-term applications.
Innovation Solution
Molecular feedback circuits with latent deactivation domains are introduced, allowing for the modulation of signaling pathways within cells through nucleic acids that encode switch polypeptides, enabling self-regulation and sustained output without external stimuli.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If repeated external inputs are used to control cellular output, then desired cellular activity levels can be achieved, but the system requires continuous user intervention and external stimuli
Solution Approach 1:
The patent implements feedback circuits where cellular output is monitored and automatically regulates subsequent activity. The system uses output sensors that detect cellular product levels and feed this information back to control elements that modulate cellular behavior, enabling automatic maintenance of desired output levels without external intervention.
Solution Approach 2:
The engineered cells are equipped with self-regulating circuits that autonomously control their own output. The cells perform self-diagnosis and self-adjustment through integrated sensing and actuation mechanisms, allowing them to maintain desired functionality independently without requiring continuous external control inputs.
2Productivity
If external stimuli are continuously applied to modulate engineered cell output, then desired production levels are maintained, but the complexity of the control system increases
Solution Approach 1:
The control system is divided into modular functional components: sensing modules that detect specific output parameters, processing modules that interpret sensor data, and actuation modules that execute control decisions. Each module performs a discrete function, making the overall complex system manageable through functional segmentation and independent optimization of each component.
Solution Approach 2:
The patent employs universal control circuits that can regulate multiple different cellular outputs through a common architecture. The feedback control system is designed to handle various types of cellular products (metabolites, proteins, etc.) using the same basic control paradigm, reducing overall system complexity through multi-functionality.
3Duration of action of moving object
If external inputs are used to sustain cellular activity, then desired outputs are achieved, but the system cannot maintain output without continuous user-provided inputs
Solution Approach 1:
The feedback control circuit continuously monitors cellular output and automatically adjusts cellular activity to maintain desired levels over extended periods. The system detects deviations from target output and triggers appropriate corrective actions, enabling sustained productive operation without external intervention throughout the entire operational duration.
Solution Approach 2:
The patent implements control mechanisms that ensure continuous productive cellular activity by preventing idle periods or suboptimal states. The feedback system maintains cellular outputs within the desired range throughout operation, eliminating downtime and ensuring uninterrupted useful action from the engineered cells.
Data Source
AI summary
Provided are molecular feedback circuits as well as nucleic acids encoding such molecular feedback circuits and cells genetically modified with the subject molecular feedback circuits. Methods of modulating signaling of a signaling pathway of a cell using molecular feedback circuits and methods of treating a subject for a condition by administering a cell containing a nucleic acid that encodes a molecular feedback circuit are also provided. Aspects of the molecular feedback circuits of the present disclosure include a signaling protein, of a signaling pathway, that includes a latent deactivation domain. Such circuits may include a regulatory sequence that is responsive to an output of the signaling pathway and is operably linked to a nucleic acid encoding a switch polypeptide that, when expressed, triggers the deactivation domain to deactivate the signaling molecule.