Targeted Retrovector for Cytokine Storm Treatment

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Solution Overview

Problem

Current treatments for COVID-19 and other diseases causing tissue damage and proliferative immune cell responses are inadequate in addressing severe complications such as cytokine storm and Acute Respiratory Distress Syndrome (ARDS), which are associated with excessive immune reactions and tissue damage.

Innovation Solution

Administration of a targeted retrovector, specifically DeltaRex-G, which encodes a dominant negative cyclin G1 construct and binds to collagenous proteins, targeting and killing proliferative immune cells to reduce cytokine release and tissue damage, thereby minimizing severe complications.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional treatments are used for COVID-19, then general supportive care is provided, but severe complications such as cytokine storm and ARDS are not effectively addressed

Engineering Contradiction:

Improveeffectiveness of treatmentVSAvoidseverity of complications

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The treatment approach is segmented into two distinct components: (1) a collagen-binding targeting moiety that directs the therapeutic to sites of tissue damage, and (2) a cytocidal payload (dominant negative cyclin G1) that eliminates pathogenic proliferative immune cells. This segmentation allows the therapy to specifically address severe complications while sparing normal immune function.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The collagen-binding moiety acts as an intermediary that bridges the therapeutic agent to sites of tissue damage. By binding to exposed collagen at injury sites, it mediates the delivery of the cytocidal payload precisely where it is needed, resolving the contradiction between providing general care and targeting severe complications.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Object-affected harmful factors

If targeted retrovector is administered to kill proliferative immune cells, then cytokine release and tissue damage are reduced, but systemic toxicity may occur

Engineering Contradiction:

Improvetissue damageVSAvoidsystemic toxicity

Core Design Contradiction:

Object-affected harmful factorsVSObject-generated harmful factors

Solution Approach 1:

The retrovector is engineered with collagen-binding properties that confer local activity at sites of tissue damage. The targeting moiety ensures the cytocidal payload is delivered preferentially to injured tissues where exposed collagen serves as a binding anchor, creating local quality that eliminates pathogenic cells at the injury site while minimizing systemic distribution and toxicity.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The therapy converts the harmful exposure of collagen at injury sites into a beneficial targeting mechanism. The normally structural collagen protein, when exposed at damage sites, becomes a specific anchor for the retrovector, transforming a marker of tissue damage into a precise delivery mechanism that reduces toxicity by limiting payload release to injured areas.

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

3Productivity

If dominant negative cyclin G1 is expressed to arrest cell division, then proliferative T cells are eliminated, but off-target effects on normal cells may occur

Engineering Contradiction:

Improvereduction of pathogenic immune responseVSAvoidselectivity of cell targeting

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The cytocidal activity of dominant negative cyclin G1 is extracted from systemic circulation and localized exclusively to sites of tissue damage through the collagen-binding moiety. This extraction principle ensures the payload is delivered only where exposed collagen provides a binding target, making the cell-killing activity selective for pathogenic cells at injury sites while protecting normal cells throughout the body.

Inventive Principle:

Principle #2Taking out (Extraction)

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

DeltaRex-G effectively reduces cytokine levels and severity of ARDS by targeting and arresting the cell division cycle of proliferative T cells, with minimal systemic toxicity and improved survivability and recovery outcomes in COVID-19 patients.

Implementation Method 1

The retrovector comprises a collagen-binding motif that targets the retrovector to exposed collagenous proteins at sites of tissue damage

Methodology Applied

Scientific EffectCollagen binding: Adsorption

Implementation Method 2

The retrovector encodes a cytocidal payload, such as dominant negative cyclin G1, that transduces into the proliferative immune cells and arrests their cell division cycle

Methodology Applied

Scientific EffectCell cycle arrest:

Implementation Method 3

The retrovector is administered to the subject in need thereof and selectively transduces the dividing cells through cell division-dependent retroviral transduction

Methodology Applied

Scientific EffectRetroviral transduction:

Data Source

PatentUS20230080185A1Damage-targeted treatments of disease

Publication Date: 2023.03.16 DELTA NEXT GENE LLC

AI summary

Methods of treating viral infectious diseases such as coronavirus disease 2019 and other diseases causing organ damage in a subject are provided.Treatments include administration of a targeted retrovector to the subject. Among the effects of these treatments is the lessening or prevention of complications of the disease, particularly those arising from pathogenic immune responses.