Engineered ACE2 Variants for SARS-CoV-2 Susceptibility Diagnosis

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Solution Overview

Problem

The COVID-19 pandemic poses a significant threat due to the high contagiousness and severity of SARS-CoV-2, with existing methods lacking effective means to accurately identify individual susceptibility or develop targeted treatments.

Innovation Solution

Development of rationally designed, catalytically inactive human ACE2 variants that enhance binding to the SARS-CoV-2 spike protein, potentially used as a soluble protein or in combination with an Fc domain for treatment, and methods to monitor SARS-CoV-2 infection by analyzing ACE2 polymorphisms in individuals.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If existing diagnostic methods are used for SARS-CoV-2, then general detection is possible, but accurate identification of individual susceptibility is lacking

Engineering Contradiction:

Improvesusceptibility identification accuracyVSAvoidindividual genetic variation information

Core Design Contradiction:

Measurement precisionVSLoss of information

Solution Approach 1:

The patent performs preliminary identification of ACE2 polymorphisms and susceptibility profiles before SARS-CoV-2 infection occurs. By analyzing genetic variants in advance, the system prepares personalized susceptibility assessments that enable proactive treatment planning and risk stratification before exposure or symptom development.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent segments the population into distinct susceptibility groups based on specific ACE2 polymorphisms (e.g., rs2285666, rs2074356, rs10008). This segmentation allows for tailored diagnostic approaches and personalized treatment strategies for each genetic subgroup, improving precision over universal diagnostic methods.

Inventive Principle:

Principle #1Segmentation

2Adaptability or versatility

If universal treatment approaches are used for COVID-19, then broad applicability is achieved, but personalized treatment effectiveness is reduced

Engineering Contradiction:

Improvetreatment personalizationVSAvoidtreatment effectiveness

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent changes the parameter of treatment approach based on genetically determined susceptibility profiles. By identifying specific ACE2 polymorphisms, the system adjusts treatment parameters such as antiviral selection, immunomodulator dosage, and monitoring intensity to match individual genetic characteristics, thereby improving treatment reliability through personalization.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent implements a feedback loop where treatment outcomes are monitored in relation to genetic susceptibility profiles. This feedback mechanism allows for optimization of personalized treatment protocols based on actual clinical responses, refining the relationship between genetic markers and effective interventions.

Inventive Principle:

Principle #23Feedback

3Measurement precision

If ACE2 polymorphism analysis is implemented, then personalized susceptibility prediction is enabled, but diagnostic complexity increases

Engineering Contradiction:

Improvesusceptibility prediction accuracyVSAvoidgenetic analysis system

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The patent develops a multi-functional diagnostic system that simultaneously performs multiple tasks: susceptibility prediction, risk stratification, treatment guidance, and prognosis assessment, all based on the same ACE2 polymorphism analysis. This universal approach consolidates what could be multiple separate complex systems into a single integrated platform.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent creates simplified models and algorithms that replicate complex genetic interaction patterns. By developing computational models that copy and simulate the relationships between ACE2 polymorphisms and susceptibility, the system manages analytical complexity through information processing rather than physical complexity.

Inventive Principle:

Principle #26Copying

4Object-affected harmful factors

If catalytically inactive ACE2 variants are developed, then neutralizing drug capability is enhanced, but enzymatic function is lost

Engineering Contradiction:

Improveviral neutralizationVSAvoidenzymatic activity

Core Design Contradiction:

Object-affected harmful factorsVSReliability

Solution Approach 1:

The patent extracts the viral binding and neutralization function from the ACE2 protein while deliberately removing or inactivating the catalytic domain. By separating these functions, the engineered ACE2 variants serve exclusively as decoy receptors that bind SARS-CoV-2 spike protein with high affinity without performing enzymatic cleavage, thereby enhancing neutralization while eliminating unwanted enzymatic activity.

Inventive Principle:

Principle #2Taking out (Extraction)

Data Source

PatentUS20230203466A1Ace2 receptor polymorphisms and varying susceptibility to SARS-cov-2, methods for diagnosis and treatment

Publication Date: 2023.06.29 MEDGENOME

AI summary

Human ACE2 variants are provided including methods of use thereof. The ACE2 receptor variants may be used for diagnosis and treatment of COVID-19.