RNA Oligonucleotide Helical Bend Structure for Immune Enhancement

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Solution Overview

Problem

Current RNA oligonucleotides with triphosphate groups at the 5′-end are effective in enhancing interferon expression, but there is a need for alternative sequences and structures that can also increase interferon-β or ISG56 expression without relying on triphosphate groups.

Innovation Solution

Development of RNA oligonucleotides with specific base sequences (e.g., 5′-N1GUAGAN2N3-3′ and 5′-N4N5UUUGCN6-3′) that form double strands with a helical bend structure and have a hydroxy group at the 5′-end, potentially forming hairpin structures, to enhance immune responses.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If RNA oligonucleotides with triphosphate groups at the 5′-end are used, then interferon expression is enhanced, but the structure becomes more complex and requires additional chemical modifications

Engineering Contradiction:
Improveinterferon expression enhancementVSAvoidRNA structure complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and removes the triphosphate group from the 5′-end of the RNA oligonucleotide, demonstrating that this complex chemical modification is not necessary for interferon expression enhancement. The simplified structure without triphosphate groups maintains the desired immunostimulatory effect while reducing structural complexity and chemical modification requirements.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

Instead of using RNA with triphosphate groups (conventional approach), the patent inverts the approach by using RNA with hydroxy groups at the 5′-end. This inversion of the chemical group at the 5′-position achieves the same or better interferon expression enhancement without the complexity of triphosphate modifications.

Inventive Principle:
Principle #13The other way round (Inversion)

2Reliability

If specific base sequences forming double strands with helical bend structure are used, then immune response enhancement is achieved, but the manufacturing precision requirements increase

Engineering Contradiction:
Improveimmune response enhancementVSAvoidsequence structure precision
Core Design Contradiction:
ReliabilityVSManufacturing precision

Solution Approach 1:

The patent changes the structural parameters of the RNA oligonucleotide by introducing specific base sequences (GUAG and UUUG motifs) that spontaneously form double strands with helical bend structures. This parameter change in sequence composition leads to the desired immune response enhancement while the spontaneous folding reduces the need for precise manufacturing control compared to maintaining fixed three-dimensional structures.

Inventive Principle:
Principle #35Parameter changes

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

These RNA oligonucleotides significantly increase the expression of interferon-β and ISG56, demonstrating their potential as immune system enhancers by stimulating immune responses effectively.

Implementation Method 1

the base sequences are bound to each other by a complementary binding to form double strands having a helical bend structure

Methodology Applied
Scientific EffectComplementary binding: Chemical Bonding

Implementation Method 2

These RNA oligonucleotides significantly increase the expression of interferon-β and ISG56, demonstrating their potential as immune system enhancers by stimulating immune responses effectively

Methodology Applied
Scientific EffectImmune system enhancement:

Data Source

PatentUS10174327B2RNA oligonucleotide and immune system enhancer comprising same
Publication Date: 2019.01.08 KOREA ADVANCED INST OF SCI & TECH
  • US10174327B2 patent drawing
  • US10174327B2 patent drawing
  • US10174327B2 patent drawing

AI summary

The present disclosure provides an RNA oligonucleotide having a helical bend structure and a use thereof. Specifically, double strands formed by a complementary binding of two sequences have a helical bend structure in the RNA oligonucleotide. The RNA oligonucleotide can increase the expression of interferon-β or ISG56 and thus can be used as an immune system enhancer.