Chemical Reprogramming of Non-Neuronal Cells to Neuronal Progenitors

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Solution Overview

Problem

Current cell reprogramming methods are inefficient and require genetic engineering, which introduces concerns about genetic mutations and are labor and time intensive.

Innovation Solution

A composition comprising agents such as GSK3 inhibitors, WNT agonists, ALK4/5/7 inhibitors, HDAC inhibitors, p300 activators, PDE4 inhibitors, Adenylyl cyclase agonists, retinoic acid receptor γ agonists, 5-HT3 antagonists, and metabotropic glutamate receptor agonists is used to reprogram differentiated non-neuronal cells into neuronal progenitor and mature neuronal cells without genetic manipulation, utilizing chemical means for in vitro culture or administration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If genetic engineering methods are used to reprogram cells, then reprogramming efficiency can be improved, but the risk of genetic mutations increases

Engineering Contradiction:

Improvereprogramming efficiencyVSAvoidgenetic mutation risk

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent replaces genetic engineering methods (biological/mechanical system) with small molecule chemical compounds (chemical system) to achieve cellular reprogramming. This substitution eliminates the need for viral transduction and genetic manipulation while maintaining reprogramming efficiency, thereby resolving the contradiction between productivity and safety.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent uses small molecule compounds that can reversibly modify cellular parameters such as histone modifications, DNA methylation, and protein phosphorylation states. These parameter changes enable transient and controllable reprogramming without permanent genetic alterations, reducing mutation risk while maintaining efficiency.

Inventive Principle:

Principle #35Parameter changes

2Adaptability or versatility

If traditional reprogramming methods are used, then cell type conversion can be achieved, but the process is labor intensive and time consuming

Engineering Contradiction:

Improvecell type conversion capabilityVSAvoidreprogramming time

Core Design Contradiction:

Adaptability or versatilityVSLoss of time

Solution Approach 1:

The patent extracts and isolates the essential reprogramming function into specific small molecule compounds that can be directly applied to cells. This extraction eliminates the need for complex genetic engineering procedures, reducing both labor intensity and time requirements while maintaining conversion capability.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The small molecule compounds are designed to preliminarily activate or inhibit specific signaling pathways and epigenetic modifiers that prepare cells for reprogramming. This preliminary chemical action accelerates the overall process by pre-conditioning cells before full differentiation occurs, reducing total reprogramming time.

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS10500232B2Small molecule cellular reprogramming to generate neuronal cells

Publication Date: 2019.12.10 THE J DAVID GLADSTONE INSTITUTES

AI summary

Compositions and methods are described herein for chemically inducing cells to change their differentiation state and become neuronal cells.