Transgenic Cell Production Agent for Innate Immunity Suppression

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Solution Overview

Problem

Existing gene introduction methods cause cell death due to innate immunity, limiting the yield of transgenic cells and requiring modified nucleosides that lose effectiveness in self-amplifying mRNA technologies.

Innovation Solution

Suppress innate immunity by inhibiting NFκB or genes related to innate immunity using inhibitors such as JSH-23 or calcitriol, and siRNA, allowing for increased transgenic cell yield without modified nucleosides.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If genes are introduced into cells, then transgenic cells are produced, but cell death occurs due to innate immunity

Engineering Contradiction:

Improveyield of transgenic cellsVSAvoidimmune response causing cell death

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent applies preliminary anti-action by pre-treating cells with inhibitors (such as NFκB inhibitors, vitamin C, vitamin E, or siRNA targeting immune-related genes) before introducing the transgene. This pre-suppression of innate immunity pathways prevents the harmful immune response from activating against the introduced gene, thereby reducing cell death and increasing the yield of viable transgenic cells.

Inventive Principle:

Principle #9Preliminary anti-action

Solution Approach 2:

The patent converts the harmful immune response into a beneficial outcome by using the same innate immunity pathways (NFκB, interferon response) that would normally cause cell death as targets for suppression. By inhibiting these pathways with specific compounds or siRNA, the harmful effect is transformed into a protective effect that enables successful transgene integration and expression.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

2Object-affected harmful factors

If modified nucleosides are used in mRNA, then immune response is reduced, but effectiveness is lost in self-amplifying mRNA technologies

Engineering Contradiction:

Improveimmune response to transgeneVSAvoidcompatibility with self-amplifying mRNA

Core Design Contradiction:

Object-affected harmful factorsVSAdaptability or versatility

Solution Approach 1:

The patent introduces small molecule inhibitors (such as vitamin C, vitamin E, NFκB inhibitors) and siRNA molecules as intermediary substances that mediate between the transgene and the immune system. These intermediaries selectively suppress immune pathways without modifying the mRNA structure, thereby maintaining compatibility with self-amplifying mRNA technologies while still reducing immune response.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent changes the approach from modifying the mRNA parameter (nucleoside composition) to modifying the cellular environment parameter (immune pathway activity). By altering the cellular state through inhibitor treatment or siRNA transfection rather than the mRNA structure itself, the solution becomes universally applicable to all mRNA types including self-amplifying variants.

Inventive Principle:

Principle #35Parameter changes

3Productivity

If cell death by innate immunity is avoided, then yield of transgenic cells increases, but additional treatment steps are required

Engineering Contradiction:

Improveyield of transgenic cellsVSAvoidcomplexity of transfection process

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent performs preliminary action by pre-treating cells with inhibitors or siRNA before transgene introduction. This advance preparation suppresses the immune pathways that would otherwise cause cell death, allowing for higher yields of viable transgenic cells without adding complex post-transfection steps.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent employs universal inhibitors (vitamin C, vitamin E, NFκB inhibitors) and broad-spectrum siRNA targets that can be applied across different cell types and transgene configurations. This multi-functional approach provides a versatile solution that works for various mRNA types and delivery methods, reducing the need for specialized protocols for each application.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enhances transgenic cell yield and efficiency by preventing immune response, reducing production time and cost, and maintaining transgene effectiveness in self-amplifying mRNA applications.

Implementation Method 1

NFκB is suppressed by adding an NFκB nuclear translocation inhibitor

Methodology Applied

Scientific EffectNFκB inhibition:

Implementation Method 2

the expression of a gene related to innate immunity is inhibited using siRNA

Methodology Applied

Scientific EffectRNA interference:

Data Source

PatentUS20250327032A1Agent for avoiding immune response of transgenic cells

Publication Date: 2025.10.23 HYPERION DRUG DISCOVERY CO LTD

AI summary

The present invention addresses the problem of avoiding an immune response caused by gene transfection. The present inventors have found, after intensive studies to solve the above problem, that it is possible to avoid apoptosis due to innate immunity and increase the number of transgenic cells by suppressing innate immunity in cells into which a gene is transfected. On the basis of this finding, further studies have been conducted to complete the present invention.