Antisense Oligonucleotides Modulating Adiponectin Expression

Solution Overview

Problem

Current methods are inadequate in effectively modulating the expression and function of Adiponectin (ADIPOQ) polynucleotides, which are crucial for treating various metabolic and cardiovascular diseases, due to limitations in targeting specific nucleic acid sequences and achieving desired therapeutic outcomes.

Innovation Solution

The use of antisense oligonucleotides, specifically designed to target natural antisense transcripts of Adiponectin (ADIPOQ) with at least 50% sequence identity, administered via subcutaneous, intramuscular, or intravenous routes, to modulate the expression and function of Adiponectin (ADIPOQ) in patient cells or tissues, utilizing modified nucleotides and delivery methods like liposomes or carrier molecules.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional methods are used to modulate Adiponectin expression, then treatment of metabolic and cardiovascular diseases is attempted, but the methods are inadequate and fail to achieve desired therapeutic outcomes

Engineering Contradiction:
Core Design Contradiction:
ReliabilityVSProductivity

Solution Approach 1:

The patent uses antisense oligonucleotides as intermediary molecules that bind to natural antisense transcripts of Adiponectin, thereby modulating Adiponectin expression. This intermediary approach allows specific targeting and effective modulation of gene expression, resolving the inadequacy of conventional methods.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Manufacturing precision

If antisense oligonucleotides are designed to target natural antisense transcripts with high sequence identity, then Adiponectin expression is effectively up-regulated, but the complexity of designing and administering these oligonucleotides increases

Engineering Contradiction:
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent employs oligonucleotides with specific local sequence characteristics (at least 50% sequence identity to natural antisense transcripts) to achieve precise targeting. This local quality approach allows effective Adiponectin up-regulation while maintaining manageable design complexity through focused sequence matching criteria.

Inventive Principle:
Principle #3Local quality

3Reliability

If antisense oligonucleotides are administered via subcutaneous, intramuscular, or intravenous routes, then Adiponectin mRNA levels are significantly increased in cells, but the need for multiple administration routes and delivery methods increases treatment complexity

Engineering Contradiction:
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent describes a universal oligonucleotide platform that can be administered through multiple routes (subcutaneous, intramuscular, intravenous) to achieve the same therapeutic effect of up-regulating Adiponectin. This multi-functional approach provides flexibility in administration while maintaining consistent therapeutic outcomes.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 significantly increases Adiponectin mRNA levels in cells, as demonstrated by real-time PCR results, providing a therapeutic means to up-regulate Adiponectin expression and potentially treat conditions related to insulin resistance, obesity, and cardiovascular diseases.

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 EffectDNA-RNA hybridization:

Implementation Method 2

Antisense nucleotides, for example, disrupt gene expression by hybridizing to target RNA, thereby interfering with RNA splicing, transcription, translation, and replication

Methodology Applied
Scientific EffectAntisense hybridization:

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

Methodology Applied
Scientific EffectRibonuclease H digestion: Enzyme

Data Source

PatentUS10316317B2Treatment of adiponectin (ADIPOQ) related diseases by inhibition of natural antisense transcript to an adiponectin (ADIPOQ)
Publication Date: 2019.06.11
  • US10316317B2 patent drawing
  • US10316317B2 patent drawing
  • US10316317B2 patent drawing

AI summary

The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of an Adiponectin (ADIPOQ), in particular, by targeting natural antisense polynucleotides of an Adiponectin (ADIPOQ). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of Adiponectins (ADIPOQ)s.