Artificial circRNA Hybridization for Repeat Expansion mRNA Structures
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Solution Overview
Problem
Current treatments for repeat expansion disorders, such as myotonic dystrophy and Huntington's disease, primarily focus on symptom management rather than addressing the underlying genetic cause, and there is a need for therapies that can act at the DNA or RNA level to disrupt the pathological secondary structures formed by nucleotide repeat expansions.
Innovation Solution
Development of artificial circular RNAs (circRNAs) that hybridize with pathological target mRNAs containing nucleotide repeat expansions, disrupting the secondary structures formed by these expansions to inhibit their pathological function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Object-affected harmful factors
If current treatments focus on symptom management, then patient comfort is improved, but the underlying genetic cause is not addressed
Solution Approach 1:
The invention extracts and targets the harmful secondary structures formed by repeat expansions in mRNA molecules. By designing artificial RNAs that specifically bind to and disrupt these pathological structures, the therapy removes the root cause of disease symptoms rather than merely managing them, thereby achieving both symptom relief and curative effect.
Solution Approach 2:
The invention uses artificial RNA molecules as intermediaries to disrupt the interaction between repeat expansions and cellular machinery. These artificial RNAs act as mediators that bind to the pathological secondary structures and prevent them from sequestering splicing factors, thereby restoring normal cellular function and addressing the underlying genetic cause.
2Reliability
If therapies act at DNA or RNA level to disrupt secondary structures, then the underlying cause is addressed, but treatment complexity increases
Solution Approach 1:
The invention uses artificial RNA molecules that copy the structure of natural RNA but are designed to specifically disrupt pathological secondary structures. These artificial RNAs replicate the functional properties of natural RNA (transcription, translation) while adding the capability to target and disrupt repeat expansion structures, achieving curative effect without excessive complexity.
Solution Approach 2:
The invention changes the parameters of RNA molecules by designing artificial RNAs with specific sequences and structures that complement and disrupt pathological secondary structures. By adjusting parameters such as RNA length, sequence composition, and structural features, the therapy achieves effective disruption of repeat expansions while maintaining manageable treatment complexity.
3Reliability
If artificial RNAs are designed to hybridize with target mRNAs, then secondary structures are disrupted, but RNA stability may be reduced
Solution Approach 1:
The invention segments the artificial RNA molecule into distinct functional regions: a hybridization region that binds to the target mRNA secondary structure and a stable core region that maintains RNA integrity. This segmentation allows the RNA to effectively disrupt pathological structures while preserving its own stability through the protected core sequence.
Solution Approach 2:
The invention creates composite RNA molecules that combine elements of stable natural RNA with disruptive artificial sequences. The artificial RNAs are constructed as composite structures integrating stable RNA backbones with specific hybridization domains, achieving both disruption effectiveness and structural stability through this composite design.
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 circRNAs effectively disrupt the secondary structures of pathological mRNAs, restoring normal splicing processes and reducing disease symptoms by altering the functionality of the target mRNA, thereby providing a direct therapeutic approach to these disorders.
Implementation Method 1
artificial RNAs suitable for disrupting by hybridization one or more secondary structures of one or more target mRNAs
Data Source
Figure 1
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Figure 2B
AI summary
The present invention relates to an artificial RNA molecule capable of hybridizing to a target mRNA, wherein the target mRNA is characterized by comprising (a) pathological nucleotide repeat expansions, and (b) at least one secondary structure, wherein the artificial RNA molecule is capable of disrupting by hybridization the secondary structure. Kits, compositions and uses thereof are also provided.