Chimeric Nucleic Acid Molecules with Non-AUG Translation Initiation
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Solution Overview
Problem
Current vaccines are limited in addressing a wide range of infectious diseases and cancers, particularly in developing countries where they are often unavailable or unaffordable, and there is a need for more efficient and manageable vaccine compositions and methods to elicit a robust cellular immune response.
Innovation Solution
A chimeric nucleic acid molecule with a multiplex translation initiation (MTI) sequence and a nucleic acid molecule encoding an antigen or antigenic epitope, utilizing non-AUG translation initiation sites to mediate translation initiation, is used to elicit a cellular immune response, either through direct administration or by incorporating it into a vector or cell, allowing for the production of multiple antigenic peptides for enhanced immune recognition.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If conventional vaccines are used, then existing diseases can be addressed, but the number of addressable diseases is limited and accessibility is poor in developing countries
Solution Approach 1:
The vaccine is segmented into modular components including a multiplex translation initiation sequence that can be combined with different antigenic peptides. This segmentation allows the same platform to address multiple diseases by simply changing the antigen component, thereby increasing versatility without requiring separate vaccine formulations for each disease.
Solution Approach 2:
The multiplex translation initiation sequence serves as a universal platform that can initiate translation of various different antigenic peptides. This multi-functional design enables a single vaccine backbone to be adapted for different pathogens and cancer targets, improving accessibility by reducing the need for multiple specialized vaccine formulations.
2Productivity
If traditional translation initiation is used, then standard protein expression occurs, but the efficiency and robustness of cellular immune response is limited
Solution Approach 1:
The patent changes the translation initiation parameters by using non-AUG initiation codons (such as CUG, GUG, or UUG) instead of the conventional AUG start codon. This parameter change in the translation initiation sequence enhances the efficiency of antigen expression and strengthens the resulting cellular immune response, as demonstrated by improved T cell activation and memory formation.
Solution Approach 2:
The multiplex translation initiation sequence is designed as a composite element that integrates multiple translation initiation sites within a single mRNA molecule. This composite structure allows for enhanced translation efficiency and robust protein expression, thereby strengthening the cellular immune response while maintaining reliability through multiple initiation pathways.
3Adaptability or versatility
If single antigenic peptide is used, then vaccine composition is simple, but immune recognition and response are insufficient
Solution Approach 1:
The vaccine employs segmentation by incorporating multiple antigenic peptides that are separately translated and assembled. Each peptide can target different epitopes or pathogens, and the segmentation allows for modular assembly of the final vaccine composition, enhancing immune recognition without requiring complete redesign of the entire vaccine platform.
Solution Approach 2:
The patent merges multiple translation initiation sequences with multiple antigenic peptides into a single integrated vaccine composition. This combining approach enables simultaneous expression of multiple antigens, thereby enhancing immune recognition capability while managing complexity through a unified molecular architecture that uses the same multiplex translation initiation platform for all peptides.
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 enables the elicitation of a robust cellular immune response, including the production of memory T cells, effectively targeting cancer or infectious diseases by administering the nucleic acid molecule and antigenic peptides in a prime-and-boost regimen, thereby providing a therapeutic or preventive measure against various diseases.
Implementation Method 1
the MTI comprises at least one non-AUG translation initiation site that mediates translation initiation of the antigen, antigenic epitope, or combination thereof
Data Source
AI summary
The present disclosure relates to nucleic acid vaccine compositions and methods for preventing or treating pathological conditions, such as cancer or infectious disease. Further, the disclosure provides methods for more efficient production of antigens via mRNA containing one or more non-conventional start codons to promote multiplex initiation of translation in eukaryotic cells.