Small Molecule Modulators of Splicing Machinery
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Solution Overview
Problem
Current therapies for modulating RNA expression, such as oligonucleotide targeting and gene therapy, face challenges in effectively regulating alternative splicing patterns associated with diseases, necessitating the development of new technologies that can target splicing processes.
Innovation Solution
Development of small molecule compounds that modulate nucleic acid splicing by binding to splicing machinery components or nucleic acids, altering splicing events to regulate gene product levels, suitable for treating various diseases including proliferative, neurological, and metabolic disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If oligonucleotide targeting is used to modulate RNA expression, then RNA expression can be regulated, but the therapy exhibits challenges in effectively regulating alternative splicing patterns
Solution Approach 1:
The patent changes the fundamental parameter of the therapeutic agent from oligonucleotides to small molecule compounds. These small molecules bind to splicing machinery components (such as snRNPs or spliceosome) and modulate splicing patterns, thereby improving effectiveness in regulating alternative splicing while simplifying the therapy modality compared to oligonucleotide-based approaches
2Reliability
If gene therapy is used to modulate RNA expression, then RNA expression can be regulated, but the therapy exhibits challenges in effectively regulating alternative splicing patterns
Solution Approach 1:
The patent changes the fundamental parameter of the therapeutic agent from gene therapy vectors to small molecule compounds. These small molecules directly bind to and modulate splicing machinery, improving effectiveness in regulating alternative splicing while eliminating the complexity associated with gene therapy delivery systems and vector design
3Adaptability or versatility
If small molecule compounds are developed to target splicing, then new technology for modulating RNA expression is achieved, but development challenges must be overcome
Solution Approach 1:
The patent employs a segmented approach to compound development by identifying and targeting specific binding sites on splicing machinery components. The small molecules are designed with specific structural segments that interact with particular snRNP or spliceosome components, enabling modular development and improving ease of manufacture while maintaining broad adaptability for modulating various RNA expression patterns
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
These compounds effectively modulate splicing events, providing therapeutic benefits for a range of diseases by altering gene product levels, thereby addressing the limitations of existing RNA expression modulation techniques.
Implementation Method 1
the compounds described herein may be used to target, and in embodiments bind or form a complex with, a nucleic acid (e.g., a pre-mRNA or nucleic acid component of a small nuclear ribonucleoprotein (snRNP) or spliceosome), a protein (e.g., a protein component of an snRNP or spliceosome, e.g., a member of the splicing machinery)
Data Source
AI summary
The present disclosure features compounds and related compositions that, inter alia, modulate nucleic acid splicing, e.g., splicing of a pre-mRNA, as well as methods of use thereof.