Stem Cell Gap Junction Delivery of Inhibitory Oligonucleotides

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Solution Overview

Problem

Existing methods for delivering nucleic acids to target cells, particularly cancer cells, are inefficient and lack effective mechanisms for high transfer rates and targeted delivery.

Innovation Solution

Utilizing mesenchymal lineage precursor or stem cells expressing specific markers to form gap junctions with target cells, enabling high-rate nucleic acid transfer and delivery of inhibitory oligonucleotides to reduce cancer cell growth, independent of connexin proteins like Cx43.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional nucleic acid delivery methods are used, then delivery can be achieved, but transfer rate is low and targeting efficiency is poor

Engineering Contradiction:

Improvenucleic acid transfer rateVSAvoiddelivery efficiency

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent uses mesenchymal stem cells as intermediary carriers to deliver nucleic acids to target cells. These stem cells are engineered to express gap junction proteins (Cx43, Cx40) that enable direct intercellular communication channels, allowing efficient nucleic acid transfer from the stem cell carrier to the target cell without conventional delivery mechanisms

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent modifies the expression levels of gap junction proteins (particularly Cx43 and Cx40) in mesenchymal stem cells to optimize nucleic acid transfer efficiency. By controlling the parameters of protein expression and gap junction formation, the system achieves high-rate nucleic acid delivery while maintaining cell viability

Inventive Principle:

Principle #35Parameter changes

2Productivity

If gap junction mediated transfer is used, then high rate nucleic acid delivery is achieved, but requires specific connexin protein expression

Engineering Contradiction:

Improvenucleic acid transfer rateVSAvoidapplicability across different target cells

Core Design Contradiction:

ProductivityVSAdaptability or versatility

Solution Approach 1:

The patent employs multiple gap junction protein isoforms (Cx43, Cx40, and other connexins) in the mesenchymal stem cells to create a universal delivery system. This multi-protein approach allows the stem cells to form gap junctions with various types of target cells expressing different connexin profiles, enhancing the versatility and broad applicability of the delivery system across different tissue types and disease models

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Reliability

If mesenchymal stem cells are used for delivery, then targeted delivery to cancer cells is achieved, but cell viability may be affected

Engineering Contradiction:

Improvetargeted delivery efficiencyVSAvoidstem cell viability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent performs preliminary engineering of mesenchymal stem cells to overexpress gap junction proteins and load them with therapeutic nucleic acids before delivery. This preliminary preparation ensures that the stem cells are optimized for high-rate transfer and can deliver sufficient therapeutic payload to cancer cells without requiring prolonged exposure or high concentrations that would compromise stem cell viability

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The mesenchymal stem cells serve as a protective intermediary that delivers the therapeutic nucleic acid payload without the nucleic acid directly contacting or damaging the stem cells. The gap junction-mediated transfer mechanism allows unidirectional or controlled bidirectional transfer that preserves stem cell integrity while achieving effective delivery to target cancer cells

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 method achieves significant reduction in cancer cell viability and growth by delivering inhibitory oligonucleotides effectively, maintaining cell viability of mesenchymal lineage precursor or stem cells during the process.

Implementation Method 1

contacting a target cell with a mesenchymal lineage precursor or stem cell expressing one or more of the markers selected from the group consisting of α1, α2, α3, α4 and α5, αv, β1 and β3, wherein said cell has been modified to introduce an oligonucleotide or a vector expressing the oligonucleotide. In an example, the contacting occurs under conditions permitting the mesenchymal lineage precursor or stem cell to form a gap junction with the target cell

Methodology Applied

Scientific EffectGap junction formation:

Implementation Method 2

whereby the oligonucleotide is delivered to the target cell by traversing the gap junction

Methodology Applied

Scientific EffectGap junction mediated transfer:

Implementation Method 3

Another advantage of using mesenchymal lineage precursor or stem cells for delivery of nucleic acids to target cells is the ability of the cells home to target tissues. The migration and adhesion capacity of mesenchymal lineage precursor or stem cells makes them particularly suitable for this purpose

Methodology Applied

Scientific EffectCell migration:

Data Source

PatentUS20260109981A1Cellular compositions and methods of treatment i

Publication Date: 2026.04.23 MESOBLAST INTERNATIONAL SARL

AI summary

The present disclosure relates to cellular compositions that are modified to introduce a nucleic acid or vector expressing the same. Such compositions may be used to deliver nucleic acid to a target cell and treat disease such as cancer.