Dub3 Protein Modulation for Stem Cell Isolation

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Solution Overview

Problem

Current methods lack effective markers for isolating and regulating pluripotent/totipotent stem cells, making it difficult to maintain their undifferentiated state and achieve homogeneous populations.

Innovation Solution

The use of the Dub3 protein, its variants, or nucleic acid molecules coding for them, or inhibitors thereof, to modulate cell differentiation by regulating ubiquitin hydrolase activity, allowing for the modulation of cell differentiation status in vitro.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Manufacturing precision

If conventional methods are used for isolating pluripotent/totipotent stem cells, then the isolation process is simple, but the purity and homogeneity of the isolated cell population cannot be achieved

Engineering Contradiction:
Improvepurity of isolated stem cell populationVSAvoidcomplexity of isolation method
Core Design Contradiction:
Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent introduces Dub3 protein as a specific marker and intermediary for identifying and isolating pluripotent/totipotent stem cells. This marker serves as a mediator between the isolation process and the target cell population, enabling precise selection without complex procedures. The Dub3 marker allows for specific binding and isolation of the desired cell type while maintaining simplicity in the isolation methodology.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Measurement precision

If pluripotency markers are used to identify undifferentiated cells, then cell identification is possible, but highly specific markers for pluripotent cells remain unidentified making homogenous population purification difficult

Engineering Contradiction:
Improvespecificity of cell differentiation markerVSAvoiddifficulty in detecting pluripotent cell markers
Core Design Contradiction:
Measurement precisionVSDifficulty of detecting and measuring

Solution Approach 1:

The patent utilizes the Dub3 marker which can be detected through specific binding interactions that produce measurable signals. The marker enables differentiation between pluripotent and differentiated cells through specific detection methods, allowing for precise identification and measurement of cell state without requiring complex detection procedures.

Inventive Principle:
Principle #32Color changes

3Reliability

If cancer stem cells are treated with conventional therapy, then treatment is straightforward, but therapy-resistant tumors cannot be effectively treated

Engineering Contradiction:
Improveefficacy of cancer treatmentVSAvoidadaptability of treatment to different cell types
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent extracts and targets the Dub3 marker specifically expressed in cancer stem cells for therapeutic intervention. By taking out the Dub3 marker as a specific target, the treatment can selectively作用于 cancer stem cells while sparing other cell types. This approach enables effective treatment of therapy-resistant tumors by specifically targeting the stem cell population that conventional therapies fail to eliminate.

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

Enables the precise modulation of cell differentiation, including the induction of pluripotency, dedifferentiation, and spontaneous differentiation, facilitating the isolation of stem cells and potentially treating therapy-resistant tumors by rendering cancer stem cells susceptible to therapy.

Implementation Method 1

Ubiquitin conjugation is mediated via an E1-E2-E3 cascade, whereas ubiquitin removal is catalyzed by deubiquitinating enzymes (DUBs).

Methodology Applied
Scientific EffectUbiquitin conjugation: Chemical Bonding

Implementation Method 2

Reversible modification of target proteins with ubiquitin regulates an assortment of signaling pathways either through proteasomal degradation or by altering the activity and/or localization of constituent proteins.

Methodology Applied
Scientific EffectProteasomal degradation: Decomposition (biological)

Implementation Method 3

DUBs catalyze the removal of ubiquitin from native conjugates, ubiquitin C-terminal extension peptides and linear poly-ubiquitin fusion or precursor proteins.

Methodology Applied
Scientific EffectDeubiquitination: Hydrolysis

Data Source

PatentEP3039034B1Cell differentiation marker and its uses
Publication Date: 2019.04.24 CENT NAT DE LA RECH SCI (C N R S)
  • EP3039034B1 patent drawingFigure 1A~1B
  • EP3039034B1 patent drawingFigure 1C~1G
  • EP3039034B1 patent drawingFigure 1H~1I

AI summary

The present invention relates to the use of Dub3 protein, a nucleic acid molecule coding for said protein, or an inhibitor of the activity and/or of the expression of said protein for modulating cell differentiation.