Sequential Gene Circuit for Precise Stem Cell Reprogramming

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Solution Overview

Problem

Existing methods for converting pluripotent stem cells into tissue-specific progenitor cells are inefficient and lack precise control over the sequential modulation of endogenous gene expression and activity levels necessary for effective cell conversion.

Innovation Solution

A heterologous genetic circuit comprising multiple gate units that modulate the expression and activity levels of distinct target endogenous genes in a sequential manner, utilizing activating moieties like guide nucleic acids and endonucleases to activate a cascade of gene regulation, ensuring each gate unit is necessary but not individually sufficient for the conversion process.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If existing methods are used for converting pluripotent stem cells into tissue-specific progenitor cells, then the conversion process can be performed, but the efficiency is low and precise control over sequential modulation of endogenous gene expression is lacking

Engineering Contradiction:

Improveconversion efficiencyVSAvoidprecise control over sequential modulation of endogenous gene expression

Core Design Contradiction:

ProductivityVSManufacturing precision

Solution Approach 1:

The patent divides the complex conversion process into multiple sequential steps, each controlled by a separate gate unit that modulates specific endogenous genes. This segmentation allows precise control over the timing and sequence of gene expression changes, thereby improving both conversion efficiency and manufacturing precision simultaneously.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent employs dynamic modulation of endogenous gene expression through sequentially activated gate units. Each gate unit dynamically adjusts the expression levels of specific genes at different time points during the conversion process, enabling precise control over the cellular transformation while maintaining high efficiency.

Inventive Principle:

Principle #15Dynamics

2Manufacturing precision

If a heterologous genetic circuit with multiple gate units is used to modulate endogenous genes sequentially, then precise control and conversion efficiency are improved, but the device complexity increases

Engineering Contradiction:

Improveprecise control over sequential modulation of endogenous gene expressionVSAvoidcomplexity of heterologous genetic circuit

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent designs gate units that can perform multiple functions: each gate unit not only modulates specific endogenous genes but also serves as a regulatory element for subsequent gate units in the sequence. This multi-functionality reduces the need for separate independent control mechanisms, thereby managing complexity while maintaining precise sequential control.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent implements a nested structure where gate units are organized in a hierarchical sequence, with each gate unit containing regulatory elements that control subsequent gate units. This nesting approach allows compact organization of the genetic circuit, reducing overall complexity while enabling precise sequential modulation of multiple endogenous genes.

Inventive Principle:

Principle #7Nested doll (Nesting)

Data Source

PatentUS20250388862A1Systems for cell programming and methods thereof

Publication Date: 2025.12.25 SYNTAX BIO INC

AI summary

Provided herein are systems of modulating gene expression and methods of use thereof for converting cells of one type to another type (e.g. reprogramming of stem cells into tissue-specific progenitor cells).