Targeted Exon Inclusion Molecules for Correcting mRNA Mis-Splicing
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Solution Overview
Problem
Current technologies are less effective in targeted inclusion methods for alternative splicing, particularly in inhibiting splicing mechanisms to correct mis-splicing of specific RNA targets.
Innovation Solution
Development of a targeted exon inclusion molecule comprising an optimized effect domain of an RNA-binding protein and an RNA-targeting moiety, which can be used to generate molecules that facilitate the production of wild-type protein to treat diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If blunt approaches of inhibiting splicing mechanisms by targeted destruction or steric inhibition of splicing signals are used, then alternative exon skipping can be achieved, but targeted exon inclusion does not function effectively
Solution Approach 1:
The patent introduces an intermediary molecule (small molecule compound) that mediates between the splicing machinery and the pre-mRNA target. This small molecule acts as a positive modulator that binds to splicing regulatory elements and promotes exon inclusion, rather than directly destroying or sterically blocking splicing signals. The intermediary approach enables effective targeted exon inclusion by recruiting endogenous splicing factors to the target site through the small molecule bridge.
2Reliability
If positive modulators for targeted exon inclusion are developed, then mis-splicing correction can be achieved, but the molecular complexity increases
Solution Approach 1:
The patent utilizes parameter changes in the small molecule compound's chemical structure to modulate its binding affinity and specificity for different splicing regulatory elements. By adjusting molecular parameters such as functional groups, stereochemistry, and molecular weight, the small molecule can be optimized to promote exon inclusion with high specificity. This approach corrects mis-splicing through controlled molecular interactions rather than complex multi-component systems.
Data Source
AI summary
Provided herein is a molecule for use in directing splicing event. More specifically, provided herein is a molecule for use in targeted exon inclusion during mRNA splicing, along with compositions and methods of using the same.