Linked KRAS Variant Peptides for Transient RNA Vaccine Immunity
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Solution Overview
Problem
DNA vaccines induce weaker immune responses and have risks of genomic insertion and oncogenesis, necessitating the development of RNA-based vaccines for KRAS variant peptides.
Innovation Solution
Development of antigenic peptides comprising multiple KRAS variant peptides, such as G12C, G12D, and G13D, linked via peptide bonds or linkers, with mRNA or DNA encoding these peptides, utilizing expression regulatory sequences and modified nucleotides for enhanced stability and immunogenicity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If DNA vaccines are used for KRAS variant peptides, then they can be delivered via various routes (intramuscular, subcutaneous, mucosal, or transdermal), but they induce weaker immune responses and have the risk of genomic insertion and oncogenesis
Solution Approach 1:
The patent changes the chemical nature of the vaccine from DNA to RNA, fundamentally altering the molecular parameter to eliminate genomic integration risks while maintaining delivery flexibility. The RNA-based vaccine uses modified nucleotides (such as pseudouridine or 5-methylcytidine) to enhance stability and immunogenicity without the safety concerns of DNA vaccines.
Solution Approach 2:
The patent employs RNA molecules that are inherently transient and do not integrate into the host genome, unlike DNA which can persist and cause oncogenesis. The RNA vaccine achieves its immunogenic effect temporarily and then degrades naturally, eliminating long-term safety risks while maintaining effective immune stimulation.
2Ease of manufacture
If DNA vaccines are used, then delivery is simplified, but immunogenicity is low and oncogenesis risk exists
Solution Approach 1:
The patent transitions from DNA to RNA as the vaccine platform, changing the molecular parameter to achieve higher immunogenicity. The RNA structure naturally triggers stronger immune responses through pattern recognition receptors, and the use of modified nucleotides further enhances both immunogenicity and stability without compromising safety.
Solution Approach 2:
The RNA-based vaccine uses transient RNA molecules that degrade after delivering their immunogenic function, avoiding the persistence and potential oncogenicity of DNA. This temporary presence achieves effective immune stimulation while eliminating long-term safety concerns.
3Adaptability or versatility
If multiple KRAS variant peptides are linked in a single antigenic peptide, then immune response coverage is expanded, but the peptide structure becomes more complex
Solution Approach 1:
The patent combines multiple KRAS variant peptides (G12C, G12D, G13D) into a single fused antigenic peptide construct. This merging approach allows simultaneous presentation of multiple epitopes to the immune system, expanding coverage across different KRAS mutations while simplifying delivery compared to administering separate vaccines for each variant.
Solution Approach 2:
The multi-variant antigenic peptide serves multiple functions by targeting several KRAS mutation types simultaneously. A single vaccine formulation can induce immune responses against G12C, G12D, and G13D variants, making the vaccine universally applicable to patients with different KRAS mutation profiles.
Data Source
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AI summary
Provided are an antigenic peptide linked to multiple KRAS variant peptides, an mRNA encoding the same, a DNA encoding the same, an immunogenic composition including an antigenic peptide linked to multiple KRAS variant peptides or an mRNA encoding the same, and a method of inducing an immune response to KRAS variant peptides in a subject.