Chimeric Aptamer-miRNA Complex for Targeted Tumor Therapy

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Solution Overview

Problem

Current cancer therapies targeting miRNAs for tumor progression face challenges due to inefficient delivery systems, leading to inadequate inhibition of metastatic spread and potential adverse side effects.

Innovation Solution

A chimeric complex comprising an aptamer directed against the AXL receptor tyrosine kinase and miR-148b, specifically designed to target and inhibit tumor cells expressing AXL, thereby reducing invasiveness and metastatic potential while minimizing impact on non-tumor cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If miRNA-based cancer therapies are used to target tumor progression, then antitumor activity is improved, but delivery efficiency is insufficient leading to inadequate inhibition of metastatic spread

Engineering Contradiction:

Improveantitumor activityVSAvoiddelivery efficiency

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent creates a chimeric complex that combines an aptamer (for target recognition and delivery) with miR-148b (for antitumor activity). This composite structure allows the complex to leverage the targeting capabilities of the aptamer and the therapeutic effects of the miRNA, thereby improving both delivery efficiency and antitumor activity simultaneously.

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The aptamer acts as an intermediary that facilitates the delivery of miR-148b to AXL-positive tumor cells. The aptamer binds to the AXL receptor on tumor cells and mediates the uptake of the chimeric complex, solving the delivery efficiency problem while maintaining the antitumor activity of the miRNA.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If miRNA-based cancer therapies are used to inhibit metastatic spread, then tumor progression is slowed, but adverse side effects occur due to lack of selectivity

Engineering Contradiction:

Improveinhibition of metastatic spreadVSAvoidadverse side effects

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The chimeric complex exhibits local quality by being selectively active only in AXL-positive tumor cells. The aptamer component provides specificity for the AXL receptor, ensuring that the antitumor activity of miR-148b is localized to target cells only, thereby reducing adverse side effects on non-tumor cells while maintaining effective inhibition of metastatic spread.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

Inventive Principle:

Principle #3Local quality

3Adaptability or versatility

If conventional delivery systems are used for miRNA therapy, then therapeutic coverage is expanded, but selectivity for tumor cells is reduced

Engineering Contradiction:

Improvetherapeutic coverageVSAvoidselectivity for tumor cells

Core Design Contradiction:

Adaptability or versatilityVSMeasurement precision

Solution Approach 1:

The aptamer serves as a selective intermediary that confers tumor cell specificity to the miR-148b therapeutic. By binding to the AXL receptor that is overexpressed on tumor cells, the aptamer ensures that the therapeutic effect is delivered selectively to the intended target, thereby maintaining both therapeutic coverage and high selectivity.

Inventive Principle:

Principle #24Intermediary (Mediator)

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 chimeric complex effectively decreases tumor cell invasiveness and metastasis in vitro and in vivo, inducing necrosis and apoptosis in AXL-positive tumor cells with minimal side effects, demonstrating targeted antitumor activity.

Implementation Method 1

an artificial aptamer molecule and an isolated, naturally occurring miRNA molecule, which are capable of performing different actions. The chimeric complex according to the invention comprises an aptamer directed towards the AXL receptor tyrosine kinase

Methodology Applied

Scientific EffectAptamer binding:

Implementation Method 2

The chimeric complex effectively decreases tumor cell invasiveness and metastasis in vitro and in vivo, inducing necrosis and apoptosis in AXL-positive tumor cells with minimal side effects

Methodology Applied

Scientific EffectApoptosis induction:

Implementation Method 3

The chimeric complex effectively decreases tumor cell invasiveness and metastasis in vitro and in vivo, inducing necrosis and apoptosis in AXL-positive tumor cells

Methodology Applied

Scientific EffectNecrosis induction:

Data Source

PatentUS20220356475A1Chimeric complex and therapeutic uses thereof

Publication Date: 2022.11.10 UNIVESITA DEGLI STUDI DI TORINO

AI summary

A chimeric complex comprising a microRNA in combination with an aptamer for AXL receptor tyrosine kinase is provided. Use of the chimeric complex for targeted treatment of a tumor disease, in particular in a therapy affecting onset and/or progression of tumor metastasis is also provided.