GPC3-Specific DNA Aptamer for Targeted HCC Therapy

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Solution Overview

Problem

Current treatments for hepatocellular carcinoma, such as sorafenib, have limited effectiveness and cause severe side effects due to non-specific targeting of proteins, and existing diagnostic methods are inadequate for early detection of atypical HCC, leading to poor prognosis and high mortality rates.

Innovation Solution

Development of a Glypican-3 (GPC3) specific DNA aptamer with a hydrophobic functional group substitution at the 5-position of deoxyuridine, which selectively binds to GPC3 protein over-expressed in hepatocellular carcinoma cells, enabling targeted treatment and diagnosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Duration of action of moving object

If sorafenib is used for HCC treatment, then survival time increases by 2-3 months, but severe side effects occur due to non-specific targeting of proteins in normal cells

Engineering Contradiction:

Improvesurvival timeVSAvoidside effects

Core Design Contradiction:

Duration of action of moving objectVSObject-affected harmful factors

Solution Approach 1:

The patent uses a Glypican-3 specific aptamer as an intermediary targeting molecule that selectively binds to GPC3 protein on HCC cell surfaces. This aptamer mediates the delivery of therapeutic agents specifically to tumor cells expressing GPC3, avoiding interaction with normal cells that do not overexpress GPC3, thereby eliminating the non-specific side effects of sorafenib while maintaining anti-cancer efficacy

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention applies local quality by creating a targeted therapeutic approach where the aptamer-conjugated drug delivers its effect locally only to HCC cells expressing GPC3. The therapeutic action is concentrated at the tumor site through specific binding to GPC3, while normal tissues lacking GPC3 overexpression remain unaffected, thus resolving the contradiction between efficacy duration and side effect severity

Inventive Principle:

Principle #3Local quality

2Ease of operation

If current imaging studies (CT/MRI) are used for HCC diagnosis, then diagnostic capability is provided, but diagnostic accuracy and sensitivity for atypical HCC are insufficient

Engineering Contradiction:

Improvediagnostic capabilityVSAvoiddiagnostic accuracy

Core Design Contradiction:

Ease of operationVSMeasurement precision

Solution Approach 1:

The patent employs fluorescently labeled Glypican-3 specific aptamers that emit detectable signals when bound to GPC3-expressing HCC cells. This fluorescent labeling enables high-contrast imaging and detection of HCC lesions, including atypical cases, with superior sensitivity and specificity compared to conventional CT/MRI, thereby improving diagnostic accuracy while maintaining operational ease

Inventive Principle:

Principle #32Color changes

Solution Approach 2:

The invention replaces the mechanical imaging systems (CT/MRI) with a molecular recognition-based detection system using aptamers. The aptamer-GPC3 binding provides highly specific molecular identification of HCC cells, substituting the indirect mechanical imaging approach with direct molecular detection, thus achieving higher diagnostic precision for both typical and atypical HCC cases

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

3Duration of action of moving object

If surgical resection or percutaneous alcohol injection is used for early HCC treatment, then long-term survival is achieved, but these treatments are not applicable to advanced stages

Engineering Contradiction:

Improvelong-term survivalVSAvoidtreatment applicability

Core Design Contradiction:

Duration of action of moving objectVSAdaptability or versatility

Solution Approach 1:

The patent develops a universal therapeutic platform based on Glypican-3 specific aptamers that can be applied across different HCC stages. The aptamer can be conjugated with various therapeutic agents (chemotherapeutic drugs, radioisotopes, immunotherapeutic molecules) to create multi-functional treatment options suitable for both early and advanced HCC, overcoming the stage-limitation of current treatments while maintaining the potential for long-term survival

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 GPC3 specific aptamer demonstrates high binding affinity and specificity to hepatocellular carcinoma cells, inhibiting cell growth, adhesion, proliferation, and metastasis, while providing enhanced diagnostic sensitivity and specificity, and reducing side effects compared to existing therapies.

Implementation Method 1

an aptamer specifically binding to a hepatocellular carcinoma-related Glypican-3 protein and comprising deoxyuridine (dU) having a hydrophobic functional group substituted at 5-position of a pyrimidine group

Methodology Applied

Scientific EffectHydrophobic interaction: Hydrophobe

Data Source

PatentUS10577609B2Glypican-3 specific aptamer and use thereof

Publication Date: 2020.03.03 POSTECH ACADEMY INDUSTRY FOUNDATION

AI summary

The present invention relates to a DNA aptamer specifically binding to a hepatocellular carcinoma-related Glypican-3 (GPC3) protein, treatment of cancers related to the Glypican-3 protein using the same, a composition for inhibiting a cancer and a composition for diagnosing a cancer comprising the same as an active ingredient.