Mutant Vaccinia Virus Strains for Tumor Selective Gene Delivery

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Solution Overview

Problem

Current gene therapy methods face challenges in achieving selective and safe delivery of therapeutic genes to tumor cells due to the safety and selectivity concerns of viral vectors, particularly in regards to viral vectors like vaccinia virus.

Innovation Solution

Development of mutant vaccinia virus strains with truncated VGF, Serpin, and Ankyrin gene sequences to reduce virulence and enhance tumor selectivity, allowing for the creation of recombinant viruses that cannot express functionally active proteins, thereby serving as safer vectors for targeted gene delivery to tumor cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If wild-type vaccinia virus is used as a vector for gene delivery, then transduction efficiency is improved, but safety and selectivity for tumor cells deteriorate

Engineering Contradiction:

Improvetransduction efficiencyVSAvoidsafety and selectivity

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts and removes specific genes (VGF, Serpin, Ankyrin) from the vaccinia virus genome to create a mutant strain. This extraction eliminates the harmful factors (uncontrolled replication, non-selective infection) while preserving the virus's ability to deliver therapeutic genes to tumor cells, thereby resolving the contradiction between transduction efficiency and safety/selectivity

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent changes the genetic parameters of the vaccinia virus by truncating specific gene sequences. This modifies the virus's biological properties to reduce virulence and enhance tumor selectivity, allowing the vector to maintain transduction capability while improving safety profile

Inventive Principle:

Principle #35Parameter changes

2Productivity

If vaccinia virus replicates in host cells, then gene expression capability is improved, but virulence increases

Engineering Contradiction:

Improvegene expression capabilityVSAvoidvirulence

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful effect of virus replication (which causes virulence) into a beneficial feature. By carefully selecting which genes to remove, the mutant virus retains its replication capability in tumor cells (enabling gene expression) while losing the ability to cause disease. The replication mechanism itself becomes beneficial for delivering and expressing therapeutic genes without the harmful consequences of wild-type virulence

Inventive Principle:

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

Data Source

PatentEP2984167B1Mutant vaccinia virus strains, uses thereof and method of producing the same

Publication Date: 2019.12.04 TOT SHANGHAI R&D CENT

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AI summary

The present disclosure provides mutant vaccinia virus strains that can selectively replicate in tumor cells. The present disclosure also provides use of the mutant vaccinia virus strains for preventing and treating tumors.