CpG-Modified Mayaro Virus for Stable Oncolytic Attenuation

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Solution Overview

Problem

Existing oncolytic viruses for cancer therapy face challenges in selectively targeting cancer cells while minimizing toxicity to normal cells, and existing methods of altering viral genomes for attenuation can lead to unpredictable reversion and instability.

Innovation Solution

A non-naturally occurring Mayaro virus is engineered with exogenous CpG dinucleotides at specific positions to enhance CpG frequency, maintaining amino acid sequence integrity and leveraging natural genomic variability for stable attenuation, which is then encapsulated in nano-particles for targeted cancer treatment.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If existing methods of altering viral genomes for attenuation are used, then viral virulence is reduced, but genome stability and predictability of attenuation deteriorate

Engineering Contradiction:

Improveviral virulenceVSAvoidgenome stability

Core Design Contradiction:

Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The patent introduces exogenous CpG dinucleotides at specific positions in the viral genome to alter the dinucleotide composition parameter. This changes the genomic parameters to achieve stable attenuation, as CpG suppression is a characteristic feature of vertebrate RNA viruses and its disruption creates predictable attenuation without compromising genome stability

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent exploits the natural phenomenon of CpG suppression in vertebrate RNA viruses by introducing exogenous CpG dinucleotides. This converts the evolutionary adaptation (CpG suppression) into a tool for creating stable attenuated viruses, where the disruption of this suppression pattern provides predictable attenuation while maintaining genome stability

Inventive Principle:

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

2Object-generated harmful factors

If existing oncolytic viruses are used to target cancer cells, then cancer cell destruction is achieved, but toxicity to normal cells increases

Engineering Contradiction:

Improvecancer cell destructionVSAvoidtoxicity to normal cells

Core Design Contradiction:

Object-generated harmful factorsVSObject-affected harmful factors

Solution Approach 1:

The patent introduces exogenous CpG dinucleotides at specific local positions in the viral genome rather than uniformly throughout. This local modification creates viruses with targeted attenuation properties that maintain selective cytotoxicity for cancer cells while reducing toxicity to normal cells, as the CpG introduction locally alters viral replication dynamics without compromising oncolytic activity

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20250381263A1Alphavirus (Mayaro virus) Constructs Attenuated for Human and Method of its Use

Publication Date: 2025.12.18 INST PASTEUR DE MONTEVIDEO

AI summary

Genetically engineered alphavirus constructs (e.g., Mayaro virus) attenuated in normal human by increasing CpG dinucleotides frequency and its oncolytic potential against lung and pancreatic cancer. The modified virus may also be used as a live attenuated vaccine against MAYV.