Small Molecule Modulators for Nucleic Acid Splicing
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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 disease, necessitating the development of small molecule compounds that can target splicing processes.
Innovation Solution
Development of compounds that modulate nucleic acid splicing by binding to splicing machinery components or nucleic acids, altering splicing events, and impacting the expression of genes or proteins, thereby addressing aberrant splicing patterns associated with diseases like cancer and neurological disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If oligonucleotide targeting or gene therapy is used to modulate RNA expression, then RNA expression can be targeted, but the ability to effectively regulate alternative splicing patterns is limited
Solution Approach 1:
The patent employs small molecule compounds with specific chemical structures (Formula I and Formula II) that differ fundamentally from oligonucleotide modalities in their chemical parameters, enabling them to interact with splicing machinery through different molecular recognition mechanisms and effectively regulate alternative splicing patterns
Solution Approach 2:
The small molecule compounds act as intermediaries that bind to splicing machinery components or nucleic acids, facilitating the regulation of splicing events and gene expression in a manner that bridges the gap between chemical compounds and biological splicing processes
2Adaptability or versatility
If small molecule compounds are developed to target splicing, then splicing regulation capability is improved, but therapeutic application complexity increases
Solution Approach 1:
The small molecule compounds are designed with broad applicability to treat multiple disease types including proliferative diseases, neurological disorders, and other conditions through a common splicing modulation mechanism, reducing the need for disease-specific therapeutic development
3Reliability
If splicing modulation is increased to alter gene product levels, then therapeutic benefit is improved, but off-target effects may increase
Solution Approach 1:
The compounds achieve selective splicing modulation by targeting specific splice sites or splicing regulatory elements with localized precision, allowing differential regulation of splicing events while minimizing broad off-target effects on other biological processes
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.