Modified CpG ODN Sequences for Stronger Vaccine Adjuvant Response
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Solution Overview
Problem
Current applications of CpG ODNs are limited in clinical use due to the need for more effective sequence structures to enhance their immunostimulatory effects and broaden their application in treating infectious diseases, tumors, and allergic diseases safely and efficiently.
Innovation Solution
Development of immunoregulatory CpG ODNs with novel nucleotide sequences (SEQ ID NO: 1-6) featuring chemically modified nucleotides, particularly phosphorothioated, to stimulate both mouse and human immune responses, used as vaccine adjuvants and in pharmaceutical compositions for treating tumors, infections, and allergies.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional CpG ODN sequences are used, then basic immunostimulatory activity is achieved, but the immunostimulatory effect is insufficient and clinical application is limited
Solution Approach 1:
The patent applies parameter changes by modifying the nucleotide sequence parameters of CpG ODN, specifically optimizing the 6-nucleotide core motif structure and adjusting flanking sequences to enhance immunostimulatory activity. The invention also modifies chemical parameters through phosphorothioate backbone modification and various nucleobase modifications (fluorine substitution, methylation, etc.) to improve stability and biological activity, thereby resolving the contradiction between basic immunostimulatory activity and clinical application efficiency
Solution Approach 2:
The patent employs composite materials by combining multiple modification strategies: phosphorothioate backbone modification combined with various nucleobase modifications (fluorine substitution at specific positions, methylation, etc.), and integrating different sequence motifs (TCG repeats, GTCGTC motifs) to create a composite modified CpG ODN structure that achieves enhanced immunostimulatory effects and broadens clinical application
2Reliability
If CpG ODN sequences are modified to enhance immunostimulatory activity, then immune response is improved, but sequence design complexity increases
Solution Approach 1:
The patent applies local quality by making targeted modifications at specific locations within the CpG ODN sequence. The invention focuses on modifying the 6-nucleotide core motif (positions 1-6) and specific flanking regions, rather than randomly modifying the entire sequence. Specific nucleobases at defined positions are modified (e.g., fluorine substitution at position 2 or 5, methylation at specific locations) to achieve localized enhancement of immunostimulatory activity while maintaining overall sequence functionality
Solution Approach 2:
The patent employs segmentation by dividing the CpG ODN sequence into functional segments: the 6-nucleotide core motif (5'-X1-X2-CG-Y1-Y2-3') that provides basic immunostimulatory activity, flanking sequences that modulate activity, and specific modification sites (such as TCG repeats or GTCGTC motifs) that enhance response. This segmented approach allows independent optimization of each segment's contribution to immune response, simplifying the overall design process
3Reliability
If multiple nucleotide modifications are applied to CpG ODN, then stability and activity are enhanced, but manufacturing complexity increases
Solution Approach 1:
The patent applies preliminary action by incorporating modifications during the synthesis process rather than performing them as separate post-synthesis steps. The phosphorothioate backbone modification and specific nucleobase modifications (fluorine substitution, methylation) are integrated into the oligonucleotide synthesis procedure, allowing these modifications to be made in advance during manufacturing. This approach enhances stability and activity while avoiding complex post-synthesis modification steps
Data Source
AI summary
Provided are an immunomodulatory CpG ODN chemically modified by means of a structure as shown by general formula I and the use thereof. The CpG ODN has an immunostimulatory activity, can stimulate the proliferation of B cells, and produce specific cytokines. The above-mentioned CpG ODN can be used as a vaccine adjuvant alone or in combination with other adjuvants to exert a synergistic effect, and can also be used in the preparation of drugs for preventing or treating tumors, infections, and allergies.