GlXmGn Nucleic Acid Adjuvants for Safer Immune Stimulation

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Solution Overview

Problem

Current adjuvants used in vaccines and pharmaceutical compositions often cause undesirable side effects, such as skin irritation, inflammation, and tissue necrosis, and fail to adequately stimulate the cellular immune response, while foreign DNA or RNA can lead to over-activation of the immune system and potential cancer risks due to persistence and integration into the host genome.

Innovation Solution

Development of nucleic acid molecules with specific formulas (GlXmGn and ClXmCn) that activate the innate immune system, acting as immune-stimulating agents or adjuvants, which are designed to be short, stable, and less likely to integrate into the host genome, thereby minimizing side effects and enhancing immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional adjuvants (aluminium hydroxide, metal oxides, synthetic oils) are used to stimulate immune response, then immune response is enhanced, but side effects such as skin irritation, inflammation, and tissue necrosis occur

Engineering Contradiction:

Improveimmune response effectivenessVSAvoidskin irritation and inflammation

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The invention changes the chemical composition parameters from conventional adjuvants (aluminium hydroxide, metal oxides, synthetic oils) to specific nucleic acid sequences (CpG motifs, poly-U sequences) that stimulate immune response through different mechanisms, thereby achieving immune enhancement without the harmful side effects of traditional adjuvants

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The invention uses composite nucleic acid structures combining multiple immune-stimulating motifs (CpG dinucleotides, poly-U sequences, specific nucleotide patterns) within a single oligonucleotide molecule, creating a multi-functional adjuvant that addresses multiple immune pathways simultaneously while avoiding the toxicities of conventional materials

Inventive Principle:

Principle #40Composite materials

2Reliability

If foreign DNA or RNA is used as immune-stimulating agent, then immune response is activated, but over-activation occurs leading to potential cancer risks due to persistence and integration into host genome

Engineering Contradiction:

Improveimmune response activationVSAvoidimmune system over-activation and cancer risk

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The invention employs short oligonucleotide sequences (typically 15-50 nucleotides) that are designed to be transient rather than persistent. These short nucleic acid molecules activate immune receptors temporarily and are rapidly degraded by cellular nucleases, preventing long-term persistence and genomic integration that could lead to cancer

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

Solution Approach 2:

The invention segments the immune-stimulating function into specific, localized nucleotide motifs (CpG dinucleotides at positions 2-4, poly-U sequences of 3-10 uracils) within short oligonucleotide carriers. This segmentation allows precise control over immune activation intensity and duration, preventing over-activation while maintaining effectiveness

Inventive Principle:

Principle #1Segmentation

3Productivity

If adjuvants are added to vaccines to increase immune response, then effectiveness is improved, but toxic side effects and tissue necroses are observed

Engineering Contradiction:

Improvevaccine effectivenessVSAvoidtoxic side effects and tissue necroses

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The invention uses specific nucleic acid sequences as intermediary molecules that bridge the antigen and the immune system. These oligonucleotides with CpG motifs and poly-U sequences act as mediators that naturally trigger immune pathways (TLR9, RIG-I-like receptors) without requiring toxic conventional adjuvants, thus improving vaccine effectiveness while avoiding tissue damage

Inventive Principle:

Principle #24Intermediary (Mediator)

Data Source

PatentUS10441653B2Nucleic acid comprising GlXmGn as an immune-stimulating agent/adjuvant

Publication Date: 2019.10.15 CUREVAC SE

AI summary

The present invention relates to a nucleic acid of the general formula (I): GIXmGn, which may be modified by a lipid. The invention relates further to a pharmaceutical composition containing an immune-stimulating agent according to the invention in combination with a pharmaceutically active carrier/vehicle (and, optionally, further auxiliary substances, additives and/or further adjuvants). The present invention can relate to a vaccine, which corresponds to a pharmaceutical composition of the invention, wherein the pharmaceutically active component induces a specific immune response (e.g. an antigen). The present invention can relate to the use of a nucleic acid of the invention or a pharmaceutical composition according to the invention for the treatment of infectious diseases, autoimmune disease, allergies or cancer diseases.