Regulatable Myc Fusion Protein Neural Stem Cell Lines

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Solution Overview

Problem

Current neural stem cell therapies for neurological disorders face challenges such as limited scalability, genetic instability, and tumorigenic potential, which hinder their clinical application and industrial viability, particularly for conditions like stroke, Huntington's disease, Alzheimer's, and traumatic brain injury.

Innovation Solution

Development of neural stem cell lines using a regulatable myc immortalizing gene that forms a fusion protein with the hormone-binding domain of a modified estrogen receptor, allowing for controlled cell growth and differentiation, ensuring safety and efficacy by terminating the immortalizing protein's function post-transplantation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If neural stem cells are used for transplantation therapy, then treatment potential for neurological disorders is improved, but tumorigenic potential and genetic instability increase

Engineering Contradiction:

Improvesafety of cell transplantationVSAvoidtumorigenic potential

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and removes the harmful immortalizing function from the cell therapy system by using a regulatable myc gene that can be turned off post-transplantation, thereby eliminating tumorigenic potential while preserving the therapeutic benefits of neural stem cell transplantation

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the regulatory state of the myc gene from constitutively active to regulatable, allowing control over cell proliferation and differentiation. This parameter change enables the cells to be expanded for therapy while preventing uncontrolled growth that would lead to tumors

Inventive Principle:

Principle #35Parameter changes

2Productivity

If neural stem cells are expanded for clinical use, then scalability is improved, but genetic stability deteriorates

Engineering Contradiction:

Improvescalability of cell productionVSAvoidgenetic stability

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent introduces dynamic control over cell proliferation through the regulatable myc gene system. Cells can be dynamically expanded when needed for clinical production, then the proliferation signal is removed to maintain genetic stability during storage and transplantation, resolving the contradiction between scalability and stability

Inventive Principle:

Principle #15Dynamics

3Productivity

If myc immortalizing gene is used to expand cell lines, then cell proliferation and scalability are improved, but tumorigenic risk increases

Engineering Contradiction:

Improvecell expansion capabilityVSAvoidtumorigenic risk

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent implements periodic activation of the myc gene during cell expansion phases, followed by deactivation during differentiation and transplantation phases. This periodic control allows beneficial cell proliferation while minimizing tumorigenic risk by limiting the duration of myc expression

Inventive Principle:

Principle #19Periodic action

Solution Approach 2:

The patent uses a regulatory intermediary system (regulatable myc gene controlled by tetracycline or similar agents) that mediates between the need for cell expansion and the need to prevent tumorigenesis. The intermediary allows controlled proliferation without the uncontrolled growth associated with constitutive myc expression

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS7666672B2Cell lines

Publication Date: 2010.02.23 RENEURON LTD

AI summary

The present invention relates to cells obtainable from cell lines having the ECACC Accession Nos 04091601, 04110301 and 04092302.