Cell Transdifferentiation via Gene Regulators for Neuronal Repair

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Solution Overview

Problem

Current treatments for diseases associated with neuronal function loss or death, such as Parkinson's disease and neurodegenerative disorders, lack effective therapeutic means to repair or regenerate neuronal cells, as the nervous system has limited self-repair ability.

Innovation Solution

A method for transdifferentiating non-neuronal cells, particularly glial cells, into neuronal cells using inhibitors or agonists that regulate the expression or activity of specific genes (e.g., RCOR1, RCOR2, RCOR3, Sin3a, HDAC1, etc.) to generate neuronal cells, and a pharmaceutical composition using gene editing proteins like CRISPR to induce this transformation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current treatment methods are used for neurodegenerative diseases, then disease progression can be alleviated, but effective therapeutic means to repair or regenerate neuronal cells are unavailable

Engineering Contradiction:

Improvetherapeutic effectivenessVSAvoidavailability of repair means

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent applies preliminary action by pre-identifying and characterizing the gene expression profiles that define neuronal cell identity before disease occurs. By establishing a molecular blueprint of neuronal cells through transcriptomic analysis, the invention creates a reference framework that can be used to guide reprogramming efforts later, enabling more effective therapeutic intervention when neuronal repair is needed

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent applies parameter changes by systematically analyzing and comparing gene expression parameters across different cell types and states. Through differential expression analysis, the invention identifies specific gene expression thresholds and patterns that distinguish neuronal from non-neuronal cells, providing quantifiable parameters that can be manipulated to drive transdifferentiation

Inventive Principle:

Principle #35Parameter changes

2Productivity

If non-neuronal cells are transdifferentiated into neuronal cells using gene regulation, then neuronal cell regeneration is achieved, but the method is in early stages and lacks effective means

Engineering Contradiction:

Improveneuronal cell generation efficiencyVSAvoidmethod complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent applies segmentation by dividing the complex transdifferentiation process into distinct analytical stages: (1) baseline gene expression profiling of non-neuronal cells, (2) identification of neuronal-specific differentially expressed genes, (3) validation of key regulatory genes, and (4) application of gene regulation to induce transdifferentiation. This segmented approach makes the overall complex process more manageable and systematically optimizable

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies the intermediary principle by using differentially expressed genes as molecular mediators between non-neuronal and neuronal cell states. Specifically, genes like ASH1L, KDM1A, and other epigenetic regulators serve as intermediate targets that, when modulated, facilitate the transition from glial cell gene expression patterns to neuronal gene expression patterns without requiring direct manipulation of all neuronal genes

Inventive Principle:

Principle #24Intermediary (Mediator)

3Manufacturing precision

If gene expression is regulated to induce transdifferentiation, then glial cells transform into neurons, but specific gene targets and mechanisms need to be identified

Engineering Contradiction:

Improvetransdifferentiation specificityVSAvoidgene target identification

Core Design Contradiction:

Manufacturing precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent applies mechanics substitution by replacing traditional mechanical or phenotypic methods of cell identification with molecular-level detection. Through RNA sequencing and differential expression analysis, the invention detects and measures gene expression changes at the molecular level, providing precise identification of transdifferentiation events and gene targets without relying on morphological or functional assays alone

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent applies copying by creating a molecular copy or reference profile of neuronal cell identity through transcriptomic analysis. By establishing a gene expression signature of authentic neuronal cells, the invention creates a template against which transdifferentiation success can be measured, ensuring high specificity by comparing the regenerated cells' gene expression patterns against the established neuronal reference profile

Inventive Principle:

Principle #26Copying

Data Source

PatentUS20260085284A1Method for trans-differentiating non-neuronal cells into neurons and use thereof

Publication Date: 2026.03.26 SHANGHAI GENEMAGIC BIOSCIENCES CO LTD

AI summary

Provided is a method for trans-differentiating non-neuronal cells of a mammal into neurons. The method comprises: providing a negative regulator capable of reducing the expression of negative regulatory genes, the negative regulatory gene including RCOR1, RCOR2, RCOR3, Sin3a, Sin3b, HDAC1, HDAC2, KDM1A, PHF21A, BAF53a, G9a, USP14, HuR, BrG1, EZH2, CDYL, or HMG20B; and/or providing a positive regulator capable of improving the expression of positive regulatory genes, the positive regulatory genes including DPYSL2, BAF45b, SCF, HuB, HuC, HuD, CYP1B1, or BTRC. An effective amount of the negative regulator or the positive regulator contacting the non-neuronal cells can induce trans-differentiation of the non-neuronal animal cells into neurons.