Antisense Oligonucleotides Targeting miR-133a in Osteosarcoma

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Solution Overview

Problem

Current treatments for osteosarcoma, particularly targeting cancer stem cells, are limited, with no effective targeted therapies available, and existing methods struggle to address the drug resistance and metastasis associated with CD133-expressing cells.

Innovation Solution

Administration of antisense molecules specific to miR-1, miR-10b, and miR-133a, which are upregulated in CD133-expressing osteosarcoma cells, to inhibit their expression and reduce chemoresistance and invasiveness, combined with conventional chemotherapeutic agents like cisplatin and doxorubicin.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If conventional chemotherapeutic agents are used to treat osteosarcoma, then tumor cell killing is achieved, but drug resistance develops in CD133-expressing cancer stem cells

Engineering Contradiction:

Improvechemotherapy efficacyVSAvoiddrug resistance

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The treatment approach segments the tumor population by specifically targeting CD133-expressing cancer stem cells with antisense molecules, distinguishing them from differentiated tumor cells. This segmentation allows selective intervention against the resistant subpopulation while preserving conventional chemotherapy for other cells.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

Antisense molecules serve as intermediaries that specifically bind to and inhibit miR-1, miR-10b, and miR-133a in CD133-expressing cells. These molecules mediate the suppression of chemoresistance without directly killing cells, enabling conventional chemotherapy to subsequently effective against the now-sensitive cancer stem cells.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Adaptability or versatility

If targeted therapy against cancer stem cells is developed, then drug resistance is addressed, but no effective targeted therapies are currently available for osteosarcoma

Engineering Contradiction:

Improvetargeted therapy availabilityVSAvoidtreatment effectiveness

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The invention performs preliminary action by suppressing miR-1, miR-10b, and miR-133a expression through antisense molecules before administering conventional chemotherapy. This pre-treatment modifies the cancer stem cells to make them susceptible to subsequent chemotherapy, effectively creating a targeted therapy pathway where none previously existed.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The treatment changes the biological parameters of CD133-expressing cells by suppressing specific microRNA expression levels. This parameter change (miRNA suppression) transforms the cells from a chemoresistant state to a chemosensitive state, enabling effective targeted intervention in osteosarcoma.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If antisense molecules are administered to suppress microRNA expression, then chemoresistance is reduced, but the complexity of the treatment regimen increases

Engineering Contradiction:

ImprovechemosensitivityVSAvoidtreatment regimen complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The treatment merges antisense molecule administration with conventional chemotherapy into a unified therapeutic regimen. By combining these approaches sequentially (antisense pre-treatment followed by chemotherapy), the invention simplifies the overall treatment architecture while achieving enhanced efficacy against CD133-expressing cells.

Inventive Principle:

Principle #5Merging (Combining)

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 approach effectively targets and reduces the population of CD133-expressing cells, enhancing the sensitivity of osteosarcoma cells to chemotherapy and inhibiting metastasis, thereby improving treatment outcomes for osteosarcoma patients.

Implementation Method 1

Administration of antisense molecules specific to miR-1, miR-10b, and miR-133a, which are upregulated in CD133-expressing osteosarcoma cells, to inhibit their expression

Methodology Applied

Scientific EffectComplementary base pairing:

Data Source

PatentUS11260072B2MicroRNA-based methods and assays for osteocarcinoma

Publication Date: 2022.03.01 3D-MATRIX LTD

AI summary

Provided are methods and compositions useful in the diagnosis, treatment, and monitoring of osteosarcoma. Antisense to certain microRNA (miRNA) found to be associated with cancer stem cells (CSCs) or tumor-initiating cells (TICs) of osteosarcoma are useful to suppress tumor growth and metastasis, and prolong survival. Antisense oligonucleotides to miR-133a are synergistic in combination with standard chemotherapy such as cisplatin in the treatment of osteosarcoma.