Aptamer Binds HGF Receptor to Control c-Met Activity

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Solution Overview

Problem

The production of HGF protein is costly and complicated, with challenges in quality control, and there is a need for a molecular tool to control c-Met activity, which is involved in cancer cell metastasis.

Innovation Solution

Development of an aptamer that binds to the HGF receptor, comprising specific polynucleotides with base sequences capable of inhibiting or activating HGF receptor signaling, formed into various structures such as loop, stem, and guanine quadruplex configurations.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If HGF protein is used to control c-Met activity, then the desired biological effect is achieved, but the production cost is high and quality control is complicated

Engineering Contradiction:
Improvec-Met activity controlVSAvoidproduction complexity
Core Design Contradiction:
ReliabilityVSEase of manufacture

Solution Approach 1:

The patent uses an aptamer (nucleic acid molecule) as a simplified copy or alternative to the HGF protein. The aptamer replicates the ligand-binding function of HGF by binding to c-Met receptor, thereby controlling c-Met activity without requiring complex protein production and quality control processes

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The aptamer provides a cost-effective alternative to HGF protein. Nucleic acid-based aptamers are generally cheaper to produce than proteins and can be synthesized using standard oligonucleotide synthesis methods, eliminating the need for complex expression systems and purification protocols required for protein production

Inventive Principle:
Principle #27Cheap short-living objects (Disposable)

2Reliability

If HGF protein is used to control c-Met activity, then the desired biological effect is achieved, but the production cost becomes expensive

Engineering Contradiction:
Improvec-Met activity controlVSAvoidproduction cost
Core Design Contradiction:
ReliabilityVSQuantity of substance

Solution Approach 1:

The aptamer serves as a functional copy of HGF that binds to c-Met with high affinity and specificity. This nucleic acid-based mimic allows achievement of the same biological effect (c-Met activation or inhibition) at a fraction of the cost of producing actual HGF protein

Inventive Principle:
Principle #26Copying

Solution Approach 2:

The patent changes the molecular parameter from protein (HGF) to nucleic acid (aptamer). This parameter change fundamentally alters the production economics, as nucleic acids can be synthesized in vitro using automated synthesizers without requiring cell culture, expression vectors, protein folding, or complex purification steps

Inventive Principle:
Principle #35Parameter changes

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

The aptamer effectively inhibits or activates HGF receptor signaling, providing a cost-effective solution for controlling c-Met activity and potentially inhibiting cancer cell metastasis.

Implementation Method 1

An aptamer comprising a polynucleotide of any of the following (a) to (c) and capable of binding to an HGF receptor to exhibit an activity of inhibiting the binding of HGF to the HGF receptor

Methodology Applied
Scientific EffectMolecular binding: Adsorption

Data Source

PatentUS10619161B2Aptamer capable of binding to HGF receptor
Publication Date: 2020.04.14 THE UNIV OF TOKYO
  • US10619161B2 patent drawing
  • US10619161B2 patent drawing
  • US10619161B2 patent drawing

AI summary

Provided is an aptamer including a polynucleotide of any of the following (a) to (c) and capable of binding to an HGF receptor to exhibit an activity of inhibiting the binding of HGF to the HGF receptor. (a) A polynucleotide consisting of a base sequence set forth in SEQ ID NO:1, (b) A polynucleotide consisting of a base sequence having the deletion, substitution, insertion and/or addition of one to several bases in the base sequence set forth in SEQ ID NO:1, and (c) A polynucleotide consisting of a base sequence having a sequence identity of 80% or more to the base sequence set forth in SEQ ID NO:1.