Antisense Oligonucleotides Targeting SOD1 Pre-mRNA for ALS
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Solution Overview
Problem
Current treatments for amyotrophic lateral sclerosis (ALS) associated with mutations or misfolding in the SOD1 gene are ineffective, and there is a need for a treatment that can ameliorate the effects of ALS.
Innovation Solution
The use of antisense oligonucleotides (AONs) that target the SOD1 pre-mRNA to induce alternative splicing through exon skipping, thereby reducing the expression of human SOD1. These AONs are specifically designed to bind to the SOD1 pre-mRNA, inhibiting its expression and potentially slowing disease progression in ALS.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If current treatments (riluzole, edaravone) are used for ALS, then patient survival is extended by 2-3 months, but the treatment effectiveness remains insufficient and disease progression continues
Solution Approach 1:
The patent extracts and targets the specific pathological mechanism of SOD1-mediated toxicity by using antisense oligonucleotides to selectively bind to SOD1 pre-mRNA and induce exon skipping. This extracts the harmful SOD1 protein production pathway from the complex disease process, allowing targeted intervention at the molecular level rather than relying on non-specific symptomatic treatments.
Solution Approach 2:
The invention applies preliminary action by intervening at the pre-mRNA level before the toxic SOD1 protein is synthesized. The antisense oligonucleotides bind to SOD1 pre-mRNA to prevent translation, stopping the pathological process before the harmful protein can be produced and cause neuronal damage.
2Reliability
If antisense oligonucleotides are designed to induce exon skipping in SOD1 pre-mRNA, then SOD1 expression is reduced, but the complexity of the treatment mechanism increases
Solution Approach 1:
The antisense oligonucleotides serve as intermediary molecules that mediate between the therapeutic goal (reducing SOD1 expression) and the molecular target (SOD1 pre-mRNA). These oligonucleotides bind specifically to the pre-mRNA and induce exon skipping, acting as a precise molecular mediator to achieve the desired therapeutic effect through a well-defined mechanism.
3Object-affected harmful factors
If mutant SOD1 protein is produced, then toxic gain-of-function occurs leading to neuronal damage, but complete elimination of SOD1 expression may reduce beneficial antioxidant activity
Solution Approach 1:
The patent applies local quality by selectively targeting and reducing mutant SOD1 expression through antisense oligonucleotides that bind to specific sequences in SOD1 pre-mRNA. This creates a localized effect on the pathological protein production while preserving the physiological function of normal SOD1, achieving differential regulation based on the specific molecular target.
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 administration of AONs effectively reduces SOD1 expression, which can slow disease progression and improve survival in ALS patients by addressing the toxic gain-of-function associated with mutant SOD1.
Implementation Method 1
The AONs are specifically designed to bind to the SOD1 pre-mRNA, inhibiting its expression
Data Source
AI summary
The present invention relates to antisense oligonucleotides that are complimentary to SOD1, leading to decreased expression of SOD1. Reduced expression of SOD1 is beneficial in medical disorders such as Amyotrophic Lateral Sclerosis.