Antisense Oligonucleotides Modulating EZH2-B2 RNA Interaction

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Solution Overview

Problem

Current technologies lack effective methods to modulate the mammalian stress response, particularly in addressing the interaction between EZH2 and B2 or ALU nucleic acids, which is crucial for regulating cell health, proliferation, and viability during environmental stresses and diseases like cancer.

Innovation Solution

The use of antisense oligonucleotides (ASOs) comprising locked nucleotides that bind to Alu or B2 RNA, altering their levels by promoting or blocking cleavage, thereby modulating the EZH2/B2 interaction. This approach can enhance or decrease cell health, proliferation, and viability in various stress conditions and diseases.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If EZH2 interacts with B2/Alu RNA to suppress stress genes, then cell proliferation is maintained under normal conditions, but cell viability decreases under environmental stress

Engineering Contradiction:
Improvecell proliferationVSAvoidcell viability under stress
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent applies preliminary action by using antisense oligonucleotides to pre-block the interaction between EZH2 and B2/Alu RNA before environmental stress occurs. This prevents the formation of the repressive complex that would otherwise suppress stress response genes when needed, thereby maintaining cell viability under stress while allowing normal proliferation under standard conditions.

Inventive Principle:
Principle #10Preliminary action

2Productivity

If B2/Alu RNA levels are high, then stress response is suppressed and cell proliferation is maintained, but cell survival under stress conditions deteriorates

Engineering Contradiction:
Improvecell proliferationVSAvoidenvironmental stress resistance
Core Design Contradiction:
ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent applies the taking out principle by extracting or removing B2/Alu RNA from the system using antisense oligonucleotides that bind to and promote degradation of these RNAs. This reduces their levels to prevent excessive suppression of stress genes, thereby improving environmental stress resistance while maintaining adequate cell proliferation through controlled application.

Inventive Principle:
Principle #2Taking out (Extraction)

3Stability of the object's composition

If EZH2/B2 interaction is strong, then transcriptional repression is maintained and cell growth is controlled, but stress response activation is inhibited

Engineering Contradiction:
Improvegene expression stabilityVSAvoidstress response adaptability
Core Design Contradiction:
Stability of the object's compositionVSAdaptability or versatility

Solution Approach 1:

The patent applies dynamics by creating a dynamic system where the EZH2/B2/Alu RNA interaction can be modulated in response to different conditions. Antisense oligonucleotides are used to dynamically adjust the strength of this interaction, allowing the system to transition between stable repression during normal growth and adaptive stress response when environmental challenges occur, thus achieving both stability and adaptability.

Inventive Principle:
Principle #15Dynamics

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 method effectively alters the expression levels of Alu or B2 RNA, influencing cell health and viability, and can be applied to manage environmental stresses, inflammation, infection, and cancer by modulating the stress response pathways.

Implementation Method 1

contacting the cell with an antisense oligonucleotide (ASO) comprising at least one locked nucleotide that binds to an Alu or B2 RNA

Methodology Applied
Scientific EffectNucleic acid hybridization:

Implementation Method 2

EZH2 is recruited and triggers cleavage of B2 RNA. B2 degradation in turn upregulates stress genes

Methodology Applied
Scientific EffectRNA cleavage:

Implementation Method 3

antisense oligonucleotide (ASO) comprising at least one locked nucleotide that binds to an Alu or B2 RNA

Methodology Applied
Scientific EffectLocked nucleic acid binding:

Data Source

PatentUS20250115910A1Modulating the cellular stress response
Publication Date: 2025.04.10 THE GENERAL HOSPITAL CORP
  • US20250115910A1 patent drawing
  • US20250115910A1 patent drawing
  • US20250115910A1 patent drawing

AI summary

Methods of using B2 or Alu nucleic acids, or antisense oligonucleotides that modulate the EZH2/B2 or EZH2/Alu interaction and have the capacity to alter cleavage of B2 and Alu RNA, for increasing or decreasing cell and organismal viability.