Nitroxide Antioxidant Modulation of APEX1 Gene Expression

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Solution Overview

Problem

Current methods fail to effectively address irregular gene expression levels, particularly those associated with apurinic/apyrimidinic endodeoxyribonuclease 1 (APEX1), which contribute to various diseases such as cancer and autoimmune disorders, by not adequately targeting and correcting the underlying genetic dysfunction.

Innovation Solution

Administering an effective amount of a nitroxide antioxidant, such as 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl, to human subjects with increased APEX1 expression levels, specifically in individuals over 35, to decrease the expression levels of APEX1 in skin, adipose, blood, and neuronal tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If natural control mechanisms are relied upon, then no external intervention is needed, but gene expression irregularities persist and worsen over time

Engineering Contradiction:
Improvenatural control of gene expressionVSAvoidgene expression regulation
Core Design Contradiction:
Adaptability or versatilityVSReliability

Solution Approach 1:

The patent introduces nitroxide antioxidants as intermediary substances that mediate between external treatment and the cell's natural gene expression control mechanisms. These compounds act as signaling molecules that restore the cell's ability to naturally regulate APEX1 expression without directly forcing the desired expression level, thus respecting and enhancing natural control while providing necessary external intervention

Inventive Principle:
Principle #24Intermediary (Mediator)

2Reliability

If gene expression is targeted and corrected through therapy, then disease progression is reduced, but the complexity of identifying and targeting specific genes increases

Engineering Contradiction:
Improvedisease treatment efficacyVSAvoidgene therapy complexity
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent changes the parameter of chemical environment (oxidative stress levels) rather than directly manipulating gene expression parameters. By administering nitroxide antioxidants that modify the oxidative state, the treatment indirectly but effectively controls APEX1 expression levels, avoiding the complexity of direct gene targeting while achieving reliable disease treatment

Inventive Principle:
Principle #35Parameter changes

3Object-affected harmful factors

If APEX1 expression is decreased, then cancer and autoimmune disease risk is reduced, but cellular functions requiring APEX1 activity may be compromised

Engineering Contradiction:
Improvedisease risk from APEX1 overexpressionVSAvoidbase excision repair activity
Core Design Contradiction:
Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent applies partial action by modulating APEX1 expression to an optimal level rather than completely suppressing it. The nitroxide antioxidants reduce APEX1 from pathological overexpression levels to physiological levels, maintaining sufficient activity for essential functions like base excision repair while eliminating the harmful effects of excessive expression that drive cancer and autoimmune diseases

Inventive Principle:
Principle #16Partial or excessive action

Data Source

PatentUS20220378768A1Modulating expression level of a gene encoding an apurinic/apyrimidinic endodeoxyribonuclease protein by treating a human subject with a nitroxide
Publication Date: 2022.12.01 HABASH LOUIS
  • US20220378768A1 patent drawing
  • US20220378768A1 patent drawing
  • US20220378768A1 patent drawing

AI summary

Some embodiments disclosed herein include a method for decreasing an expression level of a gene. The methods can include identifying a human subject having an increased expression level of APEX1; and administering to the human subject an effective amount of a nitroxide antioxidant, whereby expression level of the gene is decreased.