mRNA Functionalization via Hybridized RNA Oligomer

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Solution Overview

Problem

Current mRNA vaccines face challenges in stabilizing mRNA carriers, inducing efficient protein expression, and provoking inflammatory responses without the use of adjuvants, which can affect safety and efficacy.

Innovation Solution

The method involves functionalizing mRNA by allowing an RNA oligomer with a complementary sequence to hybridize with the mRNA, either alone or with additional RNA oligomers, to create a double-stranded RNA structure that is chemically modified, enhancing stability and immune induction.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If mRNA is chemically modified to improve enzyme resistance, then stability is improved, but protein translation efficiency is largely decreased

Engineering Contradiction:
Improveenzyme resistanceVSAvoidprotein translation efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The invention divides the mRNA molecule into two separate components: a modified RNA oligomer (which provides enzyme resistance when hybridized) and the coding sequence (which maintains translation efficiency). The modified RNA oligomer hybridizes to a complementary sequence on the mRNA, providing stability without interfering with the coding region's function.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The invention uses a modified RNA oligomer as an intermediary that hybridizes to the mRNA to provide enzyme resistance. This intermediary component carries the chemical modification (such as 2'-O-methyl or phosphorothioate) that protects against degradation, while the hybridization allows the mRNA to maintain its translation function.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If adjuvants are used to provoke inflammatory response, then immune induction is improved, but safety and efficacy are affected

Engineering Contradiction:
Improveimmune inductionVSAvoidsafety and efficacy
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention enables the mRNA vaccine to provoke its own inflammatory response through the hybridized modified RNA oligomer structure. The double-stranded RNA structure formed by hybridization inherently stimulates immune responses, eliminating the need for separate adjuvant components and their associated safety concerns.

Inventive Principle:
Principle #25Self-service

3Reliability

If mRNA carrier is stabilized, then enzyme resistance is improved, but protein expression efficiency is decreased

Engineering Contradiction:
Improveenzyme resistanceVSAvoidprotein expression efficiency
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The invention segments the mRNA carrier system into a hybridized complex where the modified RNA oligomer provides stability while the mRNA coding sequence remains accessible for translation. The hybridization occurs in regions that do not interfere with ribosome binding and translation initiation.

Inventive Principle:
Principle #1Segmentation

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

This approach stabilizes mRNA carriers, maintains protein expression efficiency, and induces stronger cellular and humoral immunity without the need for adjuvants, improving the safety and effectiveness of mRNA vaccines.

Implementation Method 1

allowing an RNA oligomer having a sequence complementary to an mRNA to hybridize with the mRNA

Methodology Applied
Scientific EffectHybridization:

Data Source

PatentUS20220296632A1mRNA functionalization method
Publication Date: 2022.09.22 THE UNIV OF TOKYO
  • US20220296632A1 patent drawing
  • US20220296632A1 patent drawing
  • US20220296632A1 patent drawing

AI summary

The present invention provides a functionalized mRNA including mRNA and double-stranded RNA including at least one RNA oligomer hybridized with mRNA. Functionalized mRNA is provided according to this configuration.