AdB-2/3 Fiber Multimers Open Epithelial Junctions

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Solution Overview

Problem

Current methods for treating disorders associated with epithelial tissue, such as solid tumors and inflammatory bowel diseases, face challenges in accessing therapeutic agents due to the trapping of these agents in intercellular junctions, limiting their efficacy.

Innovation Solution

Administration of AdB-2/3 fiber multimers or their functional equivalents, which bind to desmoglein-2 (DSG2) receptors, triggering the transient opening of intercellular junctions, thereby enhancing the delivery and efficacy of therapeutic, diagnostic, and imaging agents to epithelial tissues.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If therapeutic agents are administered to treat disorders of epithelial tissue, then treatment efficacy is limited, but this is because the agents are trapped in intercellular junctions and cannot access the target tissue effectively

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidaccess to target tissue
Core Design Contradiction:
ReliabilityVSEase of operation

Solution Approach 1:

The patent applies preliminary action by first administering AdB-2/3 fiber multimers to open intercellular junctions before administering the therapeutic agent. This preliminary opening of junctions creates access pathways that enable subsequent therapeutic agents to reach their targets effectively, resolving the contradiction between limited efficacy and poor tissue access

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The AdB-2/3 fiber multimers act as an intermediary substance that mediates between the therapeutic agent and the epithelial tissue. The fiber multimers bind to DSG2 receptors and trigger junction opening, serving as a bridge that enables the therapeutic agent to overcome the barrier of tight intercellular junctions and access the target tissue

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If CAR or CD46 receptors are used for adenovirus attachment, then virus entry is efficient, but these receptors are trapped in tight adherence junctions and are not accessible to ads

Engineering Contradiction:
Improvevirus attachment efficiencyVSAvoidreceptor accessibility
Core Design Contradiction:
ProductivityVSDifficulty of detecting and measuring

Solution Approach 1:

The patent uses AdB-2/3 fiber multimers to preliminarily open intercellular junctions before the adenovirus can attempt attachment. This preliminary action exposes the CAR and CD46 receptors that were previously trapped in tight junctions, enabling efficient virus attachment and entry while resolving the accessibility problem

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The invention effectively extracts or releases the CAR and CD46 receptors from their trapped state in tight adherence junctions. By triggering junction opening through DSG2 binding, the receptors are taken out of the inaccessible junctional complex and made available on the cell surface for adenovirus attachment

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

Improves the access and penetration of therapeutic agents across epithelial tissues, increasing their therapeutic, diagnostic, and imaging efficacy by disrupting intercellular junctions, allowing better targeting and distribution of treatments to previously inaccessible areas.

Implementation Method 1

AdB-2/3 fiber multimers or their functional equivalents, which bind to desmoglein-2 (DSG2) receptors, triggering the transient opening of intercellular junctions

Methodology Applied
Scientific EffectViral receptor binding:

Implementation Method 2

Ads internalize into the cell through endocytosis

Methodology Applied
Scientific EffectEndocytosis:

Data Source

PatentEP2580234B1Methods and systems for adenovirus interaction with desmoglein 2 (DSG2)
Publication Date: 2017.03.08 UNIVERSITY OF WASHINGTON THROUGH ITS CENTER FOR COMMERCIALIZATION
  • EP2580234B1 patent drawingFigure 1a~1g
  • EP2580234B1 patent drawingFigure 2a~2i
  • EP2580234B1 patent drawingFigure 3a~3g

AI summary

The present invention provides compositions and methods for treating disorders associated with epithelial tissues.