MAOB Antisense Oligomers for Selective mRNA Silencing
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for neurological and liver diseases associated with monoamine oxidase B (MAOB) expression are inadequate, as MAOB levels increase with age and contribute to oxidative stress and neuronal cell death.
Innovation Solution
Development of antisense oligomers that hybridize with the mRNA of MAOB, specifically targeting 8 to 50 nucleobases, to regulate its expression and inhibit its activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antisense oligomers are designed to hybridize with MAOB mRNA to reduce expression, then therapeutic effectiveness is improved, but specificity and off-target effects become critical challenges
Solution Approach 1:
The patent applies local quality by designing oligomers with specific sequence characteristics in different regions. The oligomers contain a central region (nucleotides 8-22) with high complementarity to target MAOB mRNA for strong binding, while flanking regions have reduced complementarity to minimize off-target binding. This spatial variation in binding affinity within the oligomer structure enables selective targeting of MAOB while reducing harmful off-target effects.
Solution Approach 2:
The patent employs parameter changes by systematically optimizing oligomer properties including length (15-25 nucleotides), GC content (40-60%), and melting temperature (55-65°C). These parameter adjustments fine-tune the oligomer's binding characteristics to achieve high specificity for MAOB mRNA while maintaining stability and reducing non-specific interactions with other RNA molecules.
2Stability of the object's composition
If oligomer length is increased to improve hybridization stability, then binding affinity is improved, but delivery and cellular uptake become more difficult
Solution Approach 1:
The patent applies partial action by using oligomers of moderate length (15-25 nucleotides) rather than full-length complementary sequences. This partial complementarity provides sufficient hybridization stability for effective gene silencing while maintaining small molecular size for efficient cellular uptake and delivery through various administration routes.
3Reliability
If oligomers target multiple regions of MAOB mRNA, then gene silencing effectiveness is improved, but off-target hybridization increases
Solution Approach 1:
The patent applies segmentation by dividing the MAOB mRNA target into multiple discrete oligomer binding sites (at least 8 distinct regions). Each oligomer is designed to bind to a specific segment with high specificity, and the combined effect of multiple oligomers achieves potent gene silencing. This segmented approach allows independent optimization of each oligomer's specificity and reduces cumulative off-target effects compared to single long oligomers.
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 antisense oligomers effectively reduce MAOB expression, providing therapeutic benefits for neurological and liver diseases by mitigating oxidative stress and neuronal damage.
Implementation Method 1
an oligomer which is capable of hybridizing with at least 8 contiguous nucleobases of the whole pre-mRNA sequence of MAOB
Data Source
AI summary
The present invention relates to antisense oligomers against monoamine oxidase B and uses thereof, and more particularly, to antisense oligomers that modulate the expression level of a gene encoding monoamine oxidase B, specifically the mRNA of the gene, or a protein encoded thereby, and uses thereof for preventing, alleviating or treating liver disease, obesity or neurological disease.