Antisense Oligonucleotides Targeting SCNA Natural Antisense Transcripts
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Solution Overview
Problem
Current methods for modulating the expression and function of SCNA genes, particularly in treating disorders associated with abnormal SCNA function, face limitations in specificity and efficacy, especially in upregulating functional sodium channels in patients with mutated versions.
Innovation Solution
The use of antisense oligonucleotides, specifically designed to target natural antisense transcripts of SCNA genes, which are administered to patient cells or tissues, either alone or in combination with other therapies, to upregulate the expression of functional sodium channels by binding to specific sequences within the SCNA genes, thereby modulating their expression and function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional methods are used to modulate SCNA gene expression, then some level of gene modulation is achieved, but the specificity and efficacy are insufficient, particularly in upregulating functional sodium channels in patients with mutated versions
Solution Approach 1:
The patent uses antisense oligonucleotides as intermediary molecules that specifically bind to natural antisense transcripts of SCNA genes. This intermediary approach allows precise targeting and modulation of gene expression, achieving both high specificity and effective upregulation of functional sodium channels by facilitating controlled interactions between therapeutic agents and target genes.
Solution Approach 2:
The patent employs antisense oligonucleotides with specific sequence parameters (50-90% identity to reverse complement sequences) to modulate gene expression. By optimizing parameters such as oligonucleotide length (5-30 nucleotides), sequence identity, and binding affinity, the method achieves reliable and specific upregulation of functional sodium channels while maintaining efficacy in patients with mutated versions.
2Reliability
If antisense oligonucleotides are designed to target natural antisense transcripts, then specificity of gene modulation is improved, but the complexity of the treatment approach increases
Solution Approach 1:
The patent divides the treatment approach into distinct segments: identifying natural antisense transcripts, designing specific antisense oligonucleotides with defined sequence parameters, and administering them as targeted therapy. This segmentation allows for systematic optimization of specificity while managing complexity through modular design and standardized protocols.
3Reliability
If antisense oligonucleotides are used to upregulate functional sodium channels, then neurological function is improved, but the mechanism requires precise targeting of specific sequences within SCNA genes
Solution Approach 1:
The patent replaces mechanical or broad-spectrum approaches with molecularly precise antisense oligonucleotide targeting. Instead of using non-specific methods to modulate gene expression, the invention employs sequence-specific hybridization between antisense oligonucleotides and natural antisense transcripts, enabling precise targeting of SCNA genes with defined sequences and achieving reliable upregulation of functional sodium channels.
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
This approach effectively upregulates the expression of functional sodium channels, potentially reducing the severity of SCNA-related disorders, such as Dravet's syndrome, by targeting specific sequences within the SCNA genes, thereby improving neurological function and reducing seizure frequency.
Implementation Method 1
DNA-RNA and RNA-RNA hybridization are important to many aspects of nucleic acid function including DNA replication, transcription, and translation. Antisense nucleotides, for example, disrupt gene expression by hybridizing to target RNA
Implementation Method 2
Antisense DNA has the added feature that DNA-RNA hybrids serve as a substrate for digestion by ribonuclease H
Implementation Method 3
Antisense DNA has the added feature that DNA-RNA hybrids serve as a substrate for digestion by ribonuclease H, an activity that is present in most cell types
Data Source
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AI summary
The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Sodium channel, voltage-gated, alpha subunit (SCNA), in particular, by targeting natural antisense polynucleotides of Sodium channel, voltage-gated, alpha subunit (SCNA). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of SCNA.