Artificial Nucleic Acid Molecules With Stable UTR Elements
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Solution Overview
Problem
Current gene therapy and genetic vaccination methods face challenges with the stability and translational efficiency of nucleic acid molecules, particularly RNA, which are prone to degradation and have limited expression levels due to factors like high A/T content and dependence on transcription factors.
Innovation Solution
Incorporating 3′-untranslated region (UTR) and/or 5′-untranslated region elements into artificial nucleic acid molecules, derived from stable mRNAs, to enhance protein production and translation efficiency while maintaining stability, thereby overcoming the limitations of RNA degradation and expression levels.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If RNA is used for gene therapy and genetic vaccination, then high translational efficiency and rapid protein production are achieved, but RNA stability deteriorates due to susceptibility to degradation
Solution Approach 1:
The patent modifies the nucleotide composition parameters of RNA molecules by reducing A/T content and increasing G/C content in specific regions, particularly in the 5' and 3' UTR elements. This parameter change enhances RNA stability while maintaining or improving translational efficiency, directly resolving the contradiction between RNA stability and translational efficiency
Solution Approach 2:
The patent applies different compositional requirements to different regions of the RNA molecule. Specifically, the 5' UTR and 3' UTR elements are designed with G/C content of at least 50% (preferably at least 60%), while the coding region maintains standard composition. This local quality differentiation stabilizes the RNA without compromising its translational function
2Ease of manufacture
If high A/T content is present in nucleic acid molecules, then ease of transcription and translation is improved, but molecular stability deteriorates leading to rapid degradation
Solution Approach 1:
The patent fundamentally changes the nucleotide composition parameters by requiring G/C content of at least 50% (preferably at least 60%) in the 5' and 3' UTR elements, replacing the conventional high A/T content design. This parameter change achieves both stability and translational efficiency simultaneously
3Device complexity
If conventional nucleic acid sequences are used, then simplicity of design is maintained, but expression levels deteriorate due to limited translational efficiency
Solution Approach 1:
The patent changes the compositional parameters of UTR elements to G/C content of at least 50%, which simultaneously improves expression levels and maintains design simplicity. The modified sequences are still straightforward to implement and integrate into existing gene therapy vectors
Solution Approach 2:
The patent develops universal 5' and 3' UTR elements with enhanced G/C content that can be applied to multiple different coding sequences and gene therapy applications. These universal elements improve expression levels across different genes while maintaining ease of design and implementation
Data Source
AI summary
The invention relates to an artificial nucleic acid molecule comprising at least one open reading frame and at least one 3′-untranslated region element (3′-UTR element) and/or at least one 5′-untranslated region element (5′-UTR element), wherein the at least one 3′-UTR element and/or the at least one 5′-UTR element prolongs and/or increases protein production from said artificial nucleic acid molecule and wherein the at least one 3′-UTR element and/or the at least one 5′-UTR element is derived from a stable mRNA. The invention further relates to the use of such an artificial nucleic acid molecule in gene therapy and/or genetic vaccination. Furthermore, methods for identifying a 3′-UTR element and/or a 5′-UTR derived from a stable mRNA element are disclosed.