Sequential Genetic Gate Circuits for Precise Cell Programming
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Solution Overview
Problem
Existing methods for programming cell gene expression and activity profiles are limited in their ability to achieve a desired outcome through sequential and coordinated modulation of target genes, often requiring multiple steps that individually are insufficient.
Innovation Solution
A heterologous genetic circuit comprising multiple gate units that operate in concert to induce a series of distinct modulations sequentially, with each unit necessary but insufficient alone, to achieve a desired gene expression or activity profile, including activation, disruption, or attenuation of gene regulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Manufacturing precision
If multiple gate units are used to achieve sequential and coordinated modulation of target genes, then the precision and complexity of gene expression control is improved, but the device complexity increases
Solution Approach 1:
The genetic circuit is divided into multiple discrete gate units, each responsible for a specific modulation step. This segmentation allows complex gene expression control to be achieved through coordinated action of simpler, modular components, resolving the contradiction between precision and complexity.
Solution Approach 2:
The gate units are designed to act in a predetermined sequential order, with each unit prepared to execute its specific modulation function at the appropriate time. This preliminary arrangement of functional steps enables precise temporal control of gene expression without requiring complex real-time coordination mechanisms.
2Manufacturing precision
If multiple gate units operate in concert to induce sequential modulations, then the desired gene expression profile is achieved, but the time required for the process increases
Solution Approach 1:
The gate units are designed to activate in periodic sequential steps, with each unit executing its modulation function in a timed manner. This periodic activation pattern ensures accurate gene expression profiling while optimizing the overall process time through efficient temporal organization of operations.
3Adaptability or versatility
If heterologous genetic circuits are used to program cell differentiation, then the versatility of cell programming is improved, but the ease of operation decreases
Solution Approach 1:
The gate units are designed with universal functionality that can be applied across different cell types and gene targets. Each gate unit can perform similar modulation functions on different targets, providing versatility in cell programming while maintaining operational simplicity through standardized, reusable components.
Data Source
AI summary
Provided herein are systems of modulating gene expression, methods of use thereof, and cells engineered thereof for the purpose of differentiating cells, for example immune cells.


