Chimeric Nucleic Acid Translation Activation
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current RNA therapeutics have limitations in effectively targeting and treating diseases that are untreatable through traditional therapeutic approaches, particularly those involving haploinsufficiency disorders and cancer.
Innovation Solution
Development of chimeric nucleic acids comprising a targeting region, a translational activating region, and a hairpin region, which recruit translation machinery to increase protein production from target mRNA molecules, thereby treating haploinsufficiency disorders and cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If traditional RNAi-based therapeutics are used to target disease-related mRNA, then gene expression can be suppressed, but the ability to treat haploinsufficiency disorders and cancer is limited
Solution Approach 1:
Instead of suppressing translation using RNAi, this invention inverts the approach by using antisense nucleic acids to activate and enhance translation of target mRNA. The chimeric nucleic acid combines antisense targeting with translational activation elements (IRES or eIF4G binding sites) to increase protein production rather than decrease it, thereby enabling treatment of haploinsufficiency disorders and cancer.
Solution Approach 2:
The invention changes the functional parameter of nucleic acid therapy from translation suppression to translation activation. By incorporating specific binding sites for translation initiation factors (eIF4G) or internal ribosome entry sites (IRES) into the antisense nucleic acid structure, the system transforms the outcome from protein degradation to enhanced protein synthesis, improving therapeutic effectiveness for previously untreatable conditions.
2Productivity
If chimeric nucleic acids with translational activating regions are designed, then protein production from target mRNA increases, but the nucleic acid structure becomes more complex
Solution Approach 1:
The invention merges multiple functional elements into a single chimeric nucleic acid molecule: the antisense targeting region, the translational activation region (containing IRES or eIF4G binding sites), and the hairpin structure. This combination allows one molecule to simultaneously bind target mRNA, prevent degradation, and activate translation, thereby increasing protein production without requiring multiple separate therapeutic agents.
Solution Approach 2:
The chimeric nucleic acid performs multiple functions: it acts as an antisense inhibitor to block mRNA degradation, serves as a translational activator through IRES or eIF4G binding sites to enhance protein synthesis, and provides structural stability through hairpin formation. This multi-functionality increases productivity while managing structural complexity through integrated design.
3Ease of operation
If the nucleic acid is designed to be less than 150 nucleotides, then delivery efficiency improves, but the complexity of achieving both targeting and translational activation is increased
Solution Approach 1:
The chimeric nucleic acid is segmented into distinct functional regions: a targeting region (typically 20-40 nucleotides) complementary to the mRNA, a hairpin region for structural stability, and a translational activation region containing IRES or eIF4G binding sites. This segmentation allows each region to be optimized for its specific function while maintaining overall compactness under 150 nucleotides, improving delivery efficiency.
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 described nucleic acid therapeutics effectively increase protein production from target mRNA molecules, providing a novel approach to treat haploinsufficiency disorders and cancer by enhancing translational efficiency.
Implementation Method 1
the targeting region comprises a region that is complementary to a target mRNA
Implementation Method 2
the translational activating region comprises at least one ribosome and/or translation factor binding site
Data Source
AI summary
The current disclosure relates to nucleic acid therapeutics that target mRNA molecules and recruit translation machinery to increase the translation from the mRNA, thus increasing the protein product in a subject or cell. Accordingly, aspects of the disclosure relate to a chimeric nucleic acid comprising a targeting region and a translational activating region, wherein the translational activating region comprises at least one ribosome and/or translation factor binding site and wherein the targeting region comprises a region that is complementary to a target mRNA. Further described are circular nucleic acids comprising a targeting region and a translational activating region, wherein the translational activating region comprises at least one ribosome and/or translation factor binding site and wherein the targeting region comprises a region that is complementary to a target mRNA.