Oligonucleotide Targeting Expanded Repeat Transcripts
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Solution Overview
Problem
Current methods for treating genetic disorders associated with unstable repeats, such as Huntington's disease and myotonic dystrophy, are non-selective and rely on recombinant vector delivery systems, which are costly and have safety concerns, and do not effectively target expanded repeat transcripts without affecting normal transcripts.
Innovation Solution
A short single-stranded nucleic acid molecule complementary to the expanded repeat region is used, which preferentially targets and reduces aberrant transcripts through hybridization, altering post-transcriptional processing, and can be administered directly to cells without vector-based delivery systems.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If recombinant vector delivery systems are used to treat genetic disorders with unstable repeats, then the treatment can be delivered to cells, but the cost increases and safety concerns arise
Solution Approach 1:
The patent extracts the essential function of vector delivery by using only the oligonucleotide molecule itself for direct administration to cells, eliminating the need for complex recombinant vector systems. This removes the harmful factors associated with vectors while preserving the therapeutic function.
Solution Approach 2:
The oligonucleotide acts as a direct intermediary between the therapeutic agent and the target transcript, eliminating the need for vector intermediaries. This direct approach reduces complexity and safety concerns while maintaining treatment efficacy.
2Ease of manufacture
If non-selective methods are used to reduce repeat transcripts, then the treatment approach is simpler, but normal transcripts are also affected
Solution Approach 1:
The oligonucleotide is designed with local quality specificity by targeting only the expanded repeat region with a specific sequence complementarity. This allows the treatment to affect only the abnormal transcripts while leaving normal transcripts untouched, achieving both simplicity and precision.
Solution Approach 2:
The patent exploits the parameter change in repeat length between normal and expanded transcripts. By designing the oligonucleotide to be complementary to the expanded repeat sequence, it selectively binds to and reduces only the abnormal transcripts with expanded repeats, achieving high selectivity.
3Manufacturing precision
If oligonucleotides complementary to repetitive sequences are used, then expanded repeat transcripts are selectively targeted, but the complexity of specific sequence design increases
Solution Approach 1:
The oligonucleotide design principle is universal and can be applied to any genetic disorder caused by expanded repeats. By targeting the repetitive sequence itself rather than flanking unique sequences, the same design approach works for different diseases (Huntington's, myotonic dystrophy, etc.), reducing overall design complexity through universality.
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 selectively reduces expanded repeat transcripts, minimizing impact on normal transcripts, and can be applied broadly to various unstable DNA repeat disorders, offering a safer and more effective treatment option.
Implementation Method 1
A short single-stranded nucleic acid molecule complementary to the expanded repeat region is used, which preferentially targets and reduces aberrant transcripts through hybridization
Data Source
AI summary
The current invention provides for methods and medicaments that apply oligonucleotide molecules complementary only to a repetitive sequence in a human gene transcript, for the manufacture of a medicament for the diagnosis, treatment or prevention of a cis-element repeat instability associated genetic disorders in humans. The invention hence provides a method of treatment for cis-element repeat instability associated genetic disorders. The invention also pertains to modified oligonucleotides which can be applied in method of the invention to prevent the accumulation and/or translation of repeat expanded transcripts in cells.