Genetically Modified Enterovirus Vectors With Coding-Region miRNA Targets

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Solution Overview

Problem

Current oncolytic viruses, such as Coxsackievirus B3, lack sufficient tumor specificity and genomic stability, leading to off-target toxicity and limited efficacy in treating cancers like non-small-cell lung cancer and small-cell lung cancer.

Innovation Solution

Insertion of micro-RNA (miRNA) target sequences into the UTR and coding regions of the Coxsackievirus genome to enhance tumor specificity and genomic stability, reducing off-target toxicity and increasing the virus's ability to lyse tumor cells while sparing healthy cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If miRNA target sequences are inserted into the Enterovirus genome to enhance tumor specificity, then tumor specificity is improved, but genomic stability deteriorates due to loss of target sequences over time

Engineering Contradiction:

Improvetumor specificityVSAvoidgenomic stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent changes the location parameter of miRNA target sequences from UTR regions to coding regions within the viral genome. This parameter change transforms the sequences into essential viral components that cannot be lost without compromising viral replication, thereby maintaining genomic stability while preserving tumor specificity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses the viral coding region as an intermediary carrier for the miRNA target sequences. By embedding the target sequences within essential viral genes, the sequences become protected by the selective pressure that maintains viral replicative fitness, thus preserving both genomic stability and functional effectiveness

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If oncolytic viruses are used to lyse tumor cells, then anti-cancer efficacy is improved, but off-target toxicity to normal tissues increases

Engineering Contradiction:

Improveanti-cancer efficacyVSAvoidoff-target toxicity

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality by making the virus sensitive to tissue-specific miRNA expression patterns. The viral genome contains miRNA target sequences that are selectively cleaved by miRNAs abundant in normal tissues but absent or low in tumor tissues, creating localized protection in healthy organs while maintaining lytic activity in cancer cells

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent converts the potentially harmful effect of miRNA-mediated viral degradation into a beneficial protective mechanism. By designing the virus to be sensitive to normal tissue miRNAs, the virus self-regulates by being degraded in healthy tissues (reducing toxicity) while maintaining stability and activity in tumor tissues where the protective miRNAs are absent

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Data Source

PatentUS20250304999A1Genetically modified enterovirus vectors with enhanced genomic stability

Publication Date: 2025.10.02 VIROGIN BIOTECH CANADA LTD

AI summary

A replicating oncolytic virus vector is provided having a modified Enterovirus genome (e.g., a Poliovirus, Coxsackievirus or Echovirus genome), wherein the modified Enterovirus genome has one or more copies of one or more miRNA target sequences inserted into the UTR region (e.g., via substitution) and/or in-frame within the coding region of the Enterovirus genome. Also provided are compositions and methods for treating cancer (including for example, lung cancer).