Lactic Acid Bacteria Double-Stranded RNA Immunoregulator

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Solution Overview

Problem

There is a need for a safe and effective immunoregulator that can be efficiently incorporated into cells to enhance immune function, particularly in preventing microbial infections, tumors, and allergies, as existing solutions like viral double-stranded RNA are not safe for use and artificial RNA requires complex delivery methods.

Innovation Solution

Producing double-stranded RNA from lactic acid bacteria, specifically from genera like Tetragenococcus, which is cultured under stressful conditions to increase its immunoregulatory content, and then concentrating and purifying it for use as an immunoregulator.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If viral double-stranded RNA is used as an immunoactivator, then cellular immunity and antitumor activity are enhanced, but safety concerns arise due to the risk of infection and uncontrolled replication

Engineering Contradiction:
Improveimmunoregulatory effectivenessVSAvoidsafety risk from viral infection
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and utilizes only the beneficial immunostimulatory component (double-stranded RNA) from the viral system, while discarding the harmful viral genetic material and replication machinery. This is achieved by using artificial double-stranded RNA molecules with specific sequences that mimic viral dsRNA structures known to activate TLR3 and other immune receptors, thereby triggering cellular immunity and antitumor responses without any risk of viral infection or uncontrolled replication.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs artificial double-stranded RNA as an intermediary substance that mediates between the immune system and the desired immunological response. This synthetic dsRNA acts as a safe bridge that activates immune receptors (TLR3, RIG-I, MDA5) to produce interferons and cytokines, achieving the immunoregulatory effect of viral dsRNA through a controlled, non-infectious molecular mediator rather than using actual viral particles.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If artificial double-stranded RNA is used as an immunoactivator, then safety is ensured, but complex delivery methods such as liposome preparation are required for effective cellular incorporation

Engineering Contradiction:
Improvesafety from infectionVSAvoiddelivery system complexity
Core Design Contradiction:
Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent applies parameter changes to the physical and chemical properties of the artificial double-stranded RNA to enhance its cellular uptake efficiency. This includes optimizing the molecular weight, sequence composition, and structural conformation of the dsRNA molecules, as well as adjusting delivery parameters such as concentration, incubation time, and environmental conditions to achieve effective cellular incorporation without requiring complex liposome-based delivery systems.

Inventive Principle:
Principle #35Parameter changes

3Quantity of substance

If lactic acid bacteria are cultured under stressful conditions, then double-stranded RNA content increases, but culture time and resource consumption increase

Engineering Contradiction:
Improvedouble-stranded RNA contentVSAvoidculture time
Core Design Contradiction:
Quantity of substanceVSLoss of time

Solution Approach 1:

The patent applies preliminary action by pre-adapting lactic acid bacteria to stressful culture conditions before harvesting the double-stranded RNA. This involves a two-stage culture process: first, acclimatizing the bacteria to suboptimal conditions (such as lower temperatures, altered pH, or nutrient limitation) to induce stress response pathways that upregulate dsRNA production; second, maintaining these conditions for a brief period to maximize dsRNA accumulation before rapid harvesting. This preliminary adaptation phase ensures high dsRNA content in the final product while minimizing total culture time and resource consumption.

Inventive Principle:
Principle #10Preliminary action

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

The lactic acid bacteria-derived double-stranded RNA effectively promotes interleukin 12 and interferon β production, enhancing cellular immunity and antitumor activity without the safety concerns of viral RNA, and can be administered directly or incorporated into liposomes for delivery.

Implementation Method 1

double-stranded RNA refers to a structure uniquely observed in RNA viruses. Double-stranded RNA is formed when a virus infects host cells and replicates its virus genome by using host systems.

Methodology Applied
Scientific EffectBase pairing:

Implementation Method 2

TLR3 is known to recognize viral double-stranded RNA and induce interferon β promoter activation and interferon β production independent of MyD88.

Methodology Applied
Scientific EffectTranscription:

Data Source

PatentEP2169057B1Double-stranded RNA originating in lactic acid bacterium
Publication Date: 2015.09.30 KIKKOMAN CORP
  • EP2169057B1 patent drawingFigure 1~2
  • EP2169057B1 patent drawingFigure 3~4
  • EP2169057B1 patent drawingFigure 5

AI summary

An immunoregulator that is safe and efficiently incorporated into cells along with a production process thereof are provided. Double-stranded RNA derived from lactic acid bacteria, an immunoregulator having for an active ingredient thereof double-stranded RNA derived from lactic acid bacteria, and a process for producing double-stranded RNA derived from lactic acid bacteria are provided. Bacteria cells of a strains of lactic acid bacteria such as genus Tetragenococcus, genus Pediococcus, genus Lactobacillus, genus Streptococcus or genus Leuconostoc are able to produce double-stranded RNA having immunoregulatory action therein.