Antisense Oligonucleotides Modulate TFE3 and IRS2 Expression

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Solution Overview

Problem

Current methods for modulating the expression and function of TFE3 and IRS2 polynucleotides are limited in their ability to specifically target and regulate these molecules, leading to incomplete or inefficient therapeutic outcomes in diseases related to insulin signaling and metabolic disorders.

Innovation Solution

The use of antisense oligonucleotides, specifically designed to have at least 50% sequence identity to a reverse complement of TFE3 and IRS2 polynucleotides, which are administered to patient cells or tissues to modulate the expression and function of these molecules, either up-regulating or down-regulating their activity as needed.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional methods are used to modulate TFE3 and IRS2 expression, then therapeutic outcomes are achieved, but the ability to specifically target and regulate these molecules is limited

Engineering Contradiction:
Improvespecificity of targetingVSAvoidtherapeutic effectiveness
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The patent introduces antisense oligonucleotides as intermediary molecules that specifically bind to TFE3 and IRS2 polynucleotides. These oligonucleotides act as mediators between the therapeutic agent and the target genes, enabling precise targeting through sequence-specific hybridization while maintaining therapeutic effectiveness through regulated gene expression modulation.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent employs oligonucleotides with varying degrees of sequence identity (at least 50% identity to reverse complement sequences) to modulate target gene expression. By changing parameters such as oligonucleotide length (5-30 nucleotides), sequence composition, and hybridization affinity, the system achieves both high specificity in targeting and reliable therapeutic outcomes in treating insulin signaling disorders.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If antisense oligonucleotides are used to target TFE3 and IRS2 polynucleotides, then specific regulation is achieved, but the complexity of the treatment approach increases

Engineering Contradiction:
Improvespecificity of modulationVSAvoidtreatment complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The patent divides the treatment approach into discrete oligonucleotide segments (5-30 nucleotides) that can be individually designed and synthesized to target specific regions of TFE3 and IRS2 polynucleotides. This segmentation allows for modular design where each oligonucleotide can be optimized independently for specificity while simplifying the overall treatment protocol through standardized delivery methods.

Inventive Principle:
Principle #1Segmentation

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 targets and regulates TFE3 and IRS2 polynucleotides, providing a specific and efficient means to treat diseases related to insulin signaling and metabolic disorders by altering their expression and function within patient cells or tissues.

Implementation Method 1

DNA-RNA and RNA-RNA hybridization are important to many aspects of nucleic acid function including DNA replication, transcription, and translation. Hybridization is also central to a variety of technologies that either detect a particular nucleic acid or alter its expression. Antisense nucleotides, for example, disrupt gene expression by hybridizing to target RNA

Methodology Applied
Scientific EffectHybridization:

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

Methodology Applied
Scientific EffectRibonuclease H digestion: Enzyme

Data Source

PatentEP2432882B1TREATMENT OF TRANSCRIPTION FACTOR E3 (TFE3) and INSULIN RECEPTOR SUBSTRATE 2 (IRS2) RELATED DISEASES BY INHIBITION OF NATURAL ANTISENSE TRANSCRIPT TO TFE3
Publication Date: 2019.12.25 CURNA INC
  • EP2432882B1 patent drawingFigure 1~2
  • EP2432882B1 patent drawingFigure 3
  • EP2432882B1 patent drawing

AI summary

The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Transcription factor E3 (TFE3) and/or Insulin Receptor Substrate 2 (IRS2) polynucleotides, in particular, by targeting natural antisense polynucleotides of Transcription factor E3 (TFE3) and/or Insulin Receptor Substrate 2 (IRS2). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of TFE3 and/or IRS2.