Antisense Oligonucleotides Modulate NEU4 via NAT Inhibition
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Solution Overview
Problem
Current methods for modulating the expression and function of NEU4 polynucleotides are limited in their ability to specifically target and regulate the natural antisense transcripts, leading to inefficient modulation of NEU4 activity in biological systems.
Innovation Solution
The use of antisense oligonucleotides, specifically designed to target regions with at least 50% sequence identity to the reverse complement of NEU4 polynucleotides, is employed to modulate the expression and function of NEU4 in biological systems, including patient cells or tissues, either by up-regulating or down-regulating its activity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antisense oligonucleotides are designed to target natural antisense transcripts of NEU4, then the specificity and effectiveness of NEU4 modulation is improved, but the complexity of the treatment approach increases
Solution Approach 1:
The patent uses antisense oligonucleotides as intermediary molecules that bind to natural antisense transcripts of NEU4, forming DNA-RNA hybrids. These hybrids serve as substrates for ribonuclease H, which degrades the natural antisense transcripts, thereby indirectly modulating NEU4 expression with high specificity while maintaining a relatively simple treatment mechanism
Solution Approach 2:
The patent replaces direct modulation of NEU4 with an indirect mechanism involving antisense oligonucleotides and ribonuclease H. Instead of directly targeting NEU4 mRNA or protein, the system uses oligonucleotide-mediated interference that leverages cellular enzymatic activity (ribonuclease H) to achieve specific modulation, reducing off-target effects
2Productivity
If antisense oligonucleotides are used to inhibit natural antisense transcripts, then NEU4 expression is up-regulated, but the mechanism requires additional cellular processing steps
Solution Approach 1:
The patent employs the cell's own ribonuclease H enzyme to degrade the DNA-RNA hybrids formed by the antisense oligonucleotides. Rather than requiring external degradation machinery, the system leverages the cell's inherent enzymatic activity to process and eliminate the hybrid molecules, thereby up-regulating NEU4 expression through a self-service mechanism that reduces the number of additional processing steps required
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 modulates the expression and function of NEU4, as demonstrated by increased NEU4 mRNA levels in HepG2 cells treated with phosphorothioate oligonucleotides, indicating targeted regulation of NEU4 activity.
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, an activity that is present in most cell types
Data Source
AI summary
The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Sialidase 4 (NEU4), in particular, by targeting natural antisense polynucleotides of Sialidase 4 (NEU4). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of NEU4.