Antisense Antidote Oligonucleotides for Reversing Therapeutic Activity
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Solution Overview
Problem
Current antisense compounds can have unintended side effects and prolonged activity, necessitating a means to modulate or reverse their effects, particularly in therapeutic settings where rapid adjustment of target protein levels is required.
Innovation Solution
Development of antidote compounds that are complementary to antisense compounds, specifically designed to inhibit or reverse their activity by hybridizing with them, utilizing modified oligonucleotides with phosphorothioate internucleoside linkages and 2′-O-methoxyethyl sugars, capable of activating RNase H or competing for binding sites to reduce antisense activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antisense compounds are used to modulate target nucleic acids, then therapeutic effect is improved, but side effects increase and duration of action becomes prolonged
Solution Approach 1:
The patent introduces antidote compounds as intermediary substances that mediate between the antisense compound and the target nucleic acid. The antidote compounds bind to antisense compounds to form duplexes, thereby sequestering the antisense compounds and preventing them from interacting with target mRNA. This intermediary mechanism allows for controlled reversal of antisense therapy effects, reducing unwanted side effects while maintaining therapeutic benefits.
Solution Approach 2:
The patent employs antidote compounds that can be administered to discard or neutralize the remaining active antisense compounds in the system. By administering complementary oligonucleotides that bind to and inactivate the antisense compounds, the therapeutic effect can be rapidly discontinued or adjusted, providing a mechanism to recover from unwanted or excessive therapeutic effects.
2Reliability
If antisense compounds are used to modulate target nucleic acids, then therapeutic effect is improved, but control over duration of action is reduced
Solution Approach 1:
The patent creates a dynamic system where the duration of antisense compound action can be adjusted in real-time. By administering antidote compounds at different time points and dosages, the effective duration of antisense therapy can be dynamically controlled. This allows clinicians to extend or shorten the therapeutic effect as needed, providing flexibility in treatment duration.
Solution Approach 2:
The patent establishes a feedback mechanism where the effects of antisense compounds can be monitored and reversed by administering antidote compounds. This feedback loop allows for precise control over the duration of action, enabling rapid adjustment of target protein levels in response to therapeutic needs or side effects.
3Adaptability or versatility
If rapid adjustment of target protein levels is required, then therapeutic flexibility is improved, but complexity of treatment protocol increases
Solution Approach 1:
The patent develops antidote compounds with universal applicability that can neutralize various antisense compounds through complementary base pairing. The antidote oligonucleotides can be designed to match specific antisense sequences, providing a universal reversal mechanism that works across different therapeutic targets and antisense compound types, simplifying the overall treatment approach.
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 antidote compounds effectively reduce or reverse the activity of antisense compounds, allowing for rapid adjustment of target protein levels and minimizing side effects, thereby enhancing the safety and efficacy of antisense therapies.
Implementation Method 1
antidote compounds that are complementary to antisense compounds... capable of activating RNase H or competing for binding sites to reduce antisense activity
Implementation Method 2
capable of activating RNase H or competing for binding sites to reduce antisense activity
Data Source
AI summary
The present invention relates to antisense antidote compounds and uses thereof. Such antidote compounds reduce the magnitude and/or duration of the antisense activity of an antisense compound.