Chimeric RNA Construct for Simultaneous Gene Modulation

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Solution Overview

Problem

Current therapies fail to effectively modulate gene expression to simultaneously decrease production of proteins involved in cell proliferation and angiogenesis while increasing production of proteins involved in immune response, which is crucial for preventing or treating cancer.

Innovation Solution

The development of recombinant polynucleic acid constructs that combine a cytokine-encoding RNA with a genetic element, such as siRNA, to simultaneously modulate the expression of genes associated with tumor proliferation, angiogenesis, or immune recognition, allowing for the simultaneous secretion of cytokines like IL-2 and interference with genes like VEGFA or PD-L1.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If current therapies are used to modulate gene expression, then treatment of cancer is attempted, but the ability to simultaneously decrease production of proteins involved in cell proliferation and increase production of proteins involved in immune response is insufficient

Engineering Contradiction:

Improveability to simultaneously modulate multiple gene expressionsVSAvoideffectiveness of cancer treatment

Core Design Contradiction:

Adaptability or versatilityVSReliability

Solution Approach 1:

The patent combines multiple RNA molecules (coding RNA and non-coding RNA) into a single chimeric RNA molecule that can simultaneously modulate multiple gene expressions. This merging of functions into one molecule allows simultaneous decrease of proteins involved in cell proliferation and increase of proteins involved in immune response, resolving the contradiction between versatility and reliability in cancer treatment.

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The chimeric RNA molecule is designed to perform multiple functions: it can encode a protein of interest, modulate expression of multiple target genes through integrated non-coding RNA elements, and facilitate immune response. This multi-functionality enables a single therapy to address multiple aspects of cancer pathology simultaneously, improving both adaptability and treatment effectiveness.

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Adaptability or versatility

If multiple separate therapies are used to target different gene expressions, then comprehensive cancer treatment is attempted, but device complexity and treatment protocol complexity increase

Engineering Contradiction:

Improvecomprehensive gene expression modulationVSAvoidcomplexity of therapy composition

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent merges multiple separate therapeutic RNA molecules into a single chimeric RNA structure. Instead of administering separate therapies for each gene modulation target, the invention integrates multiple functional elements (coding sequences, siRNA regions, shRNA regions, miRNA regions) into one molecule, thereby reducing treatment complexity while maintaining comprehensive gene expression modulation capability.

Inventive Principle:

Principle #5Merging (Combining)

3Quantity of substance

If separate RNAs are used for cytokine production and gene modulation, then specific functions are achieved, but manufacturing complexity and delivery complexity increase

Engineering Contradiction:

Improvecytokine productionVSAvoidmanufacturing complexity of RNA compositions

Core Design Contradiction:

Quantity of substanceVSEase of manufacture

Solution Approach 1:

The patent combines cytokine-encoding sequences and gene-modulation sequences into a single chimeric RNA molecule. This integration simplifies manufacturing processes by reducing the number of separate RNA components that need to be produced, purified, and formulated. The single RNA molecule can be transcribed from a single nucleic acid template, streamlining production while maintaining the ability to produce cytokines and modulate target gene expressions simultaneously.

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

This approach effectively increases cytokine production and decreases tumor-promoting gene expression, enhancing immune response and potentially treating various cancers by targeting specific gene pathways.

Implementation Method 1

The development of recombinant polynucleic acid constructs that combine a cytokine-encoding RNA with a genetic element, such as siRNA, to simultaneously modulate the expression of genes

Methodology Applied

Scientific EffectRNA interference:

Data Source

PatentUS20230322885A1Compositions and methods for simultaneously modulating expression of genes

Publication Date: 2023.10.12 VALAMAI LTD

AI summary

The present invention relates to compositions of recombinant polynucleic acid constructs comprising at least one nucleic acid sequence encoding an siRNA capable of binding to a target mRNA and at least one nucleic acid sequence encoding a gene of interest. Also disclosed herein is use of the compositions in treating cancers and in simultaneously modulating expression of two or more genes.