SCN2A-Targeting Oligonucleotide Compounds for RNA Reduction
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Solution Overview
Problem
There is a lack of effective treatments for neurodevelopmental disorders and intellectual disabilities associated with SCN2A mutations, such as Developmental and Epileptic Encephalopathies, Late Seizure Onset Epileptic Encephalopathy, Benign Familial Neonatal-Infantile Seizures, intellectual disability, and autism spectrum disorders, which are characterized by symptoms like seizures, motor and cognitive dysfunctions, and gastrointestinal disorders.
Innovation Solution
Development of compounds and pharmaceutical compositions that reduce the amount or activity of SCN2A RNA and protein, using modified oligonucleotides and oligomeric compounds to target and hybridize with SCN2A nucleic acid, thereby ameliorating symptoms like seizures, hypotonia, and cognitive dysfunctions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments are used for SCN2A-related disorders, then general symptom management is attempted, but effective treatment of seizures and cognitive dysfunctions is lacking
Solution Approach 1:
The patent applies parameter changes by modifying oligonucleotide structures (e.g., 2'-O-methyl modifications, phosphorothioate linkages) to enhance binding affinity and stability to SCN2A RNA, thereby improving treatment effectiveness for SCN2A-related disorders while maintaining specificity
Solution Approach 2:
The patent uses oligonucleotide compounds as intermediary molecules that specifically bind to SCN2A RNA transcripts, acting as mediators to reduce SCN2A protein expression levels and thereby treating the underlying cause of seizures and cognitive dysfunctions associated with SCN2A mutations
2Manufacturing precision
If oligonucleotide compounds are designed to specifically target SCN2A RNA, then treatment specificity is improved, but compound complexity increases
Solution Approach 1:
The patent applies local quality by introducing specific modifications at particular positions within the oligonucleotide sequence (e.g., 2'-O-methyl modifications at specific nucleotides, phosphorothioate linkages at terminal regions) to enhance binding specificity to SCN2A RNA while controlling overall molecular complexity
Solution Approach 2:
The patent segments the oligonucleotide compound into distinct functional regions: a central binding region with high complementarity to SCN2A RNA for specific targeting, and modified terminal regions for enhanced stability and pharmacokinetic properties, thereby balancing specificity with manageable complexity
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 compounds and compositions effectively reduce SCN2A RNA and protein levels, leading to improved symptoms and reduced severity or frequency of seizures, motor and cognitive dysfunctions, and other associated disorders.
Implementation Method 1
using modified oligonucleotides and oligomeric compounds to target and hybridize with SCN2A nucleic acid
Data Source
AI summary
Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of SCN2A RNA in a cell or subject, and in certain instances reducing the amount of SCN2A protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a disease or disorder associated with a voltage-gated sodium channel protein, such as, for example, a Developmental and Epileptic Encephalopathy, an intellectual disability, or an autism spectrum disorder. Such symptoms and hallmarks include, but are not limited to seizures, hypotonia, sensory integration disorders, motor development delays and dysfunctions, intellectual and cognitive dysfunctions, movement and balance dysfunctions, visual dysfunctions, delayed language and speech, gastrointestinal disorders, neurodevelopmental delays, sleep problems, and sudden unexpected death in epilepsy.