Chimeric Nucleic Acid Immunostimulating Adjuvants
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Solution Overview
Problem
Current immunostimulating agents, such as DNA and RNA, face limitations including rapid degradation, potential for anti-DNA antibody formation, integration into the host genome leading to mutations, and side effects like inflammation and cancer risk, while existing RNA molecules have limited immunostimulating capacity and induce unpredictable molecular structures.
Innovation Solution
Development of nucleic acid molecules with a specific formula (NuGlXmGnNv) that activate the innate immune system by binding to pattern recognition receptors, providing a defined length and structure for enhanced immunogenicity and stability, and can be administered in combination with other immunomodulating compounds.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If DNA or RNA molecules are used as immunostimulating agents, then immune response is activated, but rapid degradation occurs and stability is poor
Solution Approach 1:
The patent modifies the chemical parameters of nucleic acids by creating chimeric structures that combine DNA and RNA segments with specific modifications (e.g., 2'-O-methyl RNA, phosphorothioate backbones) to enhance stability while preserving immunostimulating activity. This resolves the contradiction by changing the molecular composition parameters rather than using native DNA or RNA alone.
Solution Approach 2:
The invention employs composite nucleic acid structures that integrate different nucleic acid types (DNA-RNA chimeras) with modified backbones and sugar moieties. These composite molecules combine the immunogenicity of RNA with the stability of DNA, simultaneously achieving both immune activation and molecular stability.
2Reliability
If DNA molecules are used as adjuvants, then immune response is enhanced, but integration into host genome occurs leading to mutations and cancer risk
Solution Approach 1:
The patent extracts only the immunostimulating functional elements (specific sequence motifs like CpG, GpC, GpT) from complete DNA molecules and incorporates them into modified chimeric structures that cannot integrate into the host genome. This separates the beneficial immunogenic function from the harmful integration potential.
Solution Approach 2:
The invention converts the naturally occurring immunostimulating sequences (which normally require DNA context) into modified forms within RNA-dominant chimeric structures. The modified backbones and sugar modifications prevent genomic integration while preserving the ability to activate TLR9 and other immune receptors.
3Reliability
If conventional adjuvants are used, then immune response is stimulated, but side effects such as inflammation and tissue necrosis occur
Solution Approach 1:
The patent designs nucleic acid adjuvants with controlled degradation profiles. The chimeric molecules are engineered to be transient, degrading into harmless nucleotides and nucleosides after fulfilling their immunostimulating function, avoiding the persistent inflammatory responses caused by conventional adjuvants like aluminum salts or Freund's adjuvant.
4Reliability
If RNA molecules are used for immunostimulation, then immune response is activated, but molecular structures become unpredictable
Solution Approach 1:
The patent segments RNA molecules into defined modular units with specific sequences (e.g., repeating units of 5'-GGU-3', defined stem-loop structures) and controlled lengths. This segmentation provides precise manufacturing specifications while maintaining the immunostimulating capacity associated with RNA structures.
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 nucleic acid molecules effectively stimulate the innate immune response, increasing IFN-alpha release and providing a safer, more predictable immunostimulation with reduced side effects and improved stability compared to traditional agents.
Implementation Method 1
nucleic acid molecules with a specific formula (NuGlXmGnNv) that activate the innate immune system by binding to pattern recognition receptors
Data Source
AI summary
The present invention relates to nucleic acids of the general formula (I): (NuGlXmGnNv)a and derivatives thereof as an immunostimulating agent/adjuvant and to compositions containing same, optionally comprising an additional adjuvant. The present invention furthermore relates to a pharmaceutical composition or to a vaccine, each containing nucleic acids of formula (I) above and/or derivatives thereof as an immunostimulating agent, and optionally at least one additional pharmaceutically active component, e.g. an antigenic agent. The present invention relates likewise to the use of the pharmaceutical composition or of the vaccine for the treatment of cancer diseases, infectious diseases, allergies and autoimmune diseases etc. Likewise, the present invention includes the use of nucleic acids of the general formula (I): (NuGlXmGnNv)a and/or derivatives thereof for the preparation of a pharmaceutical composition for the treatment of such diseases.