Mutant M1 Oncolytic Virus for Safer Intravenous Tumor Targeting
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Solution Overview
Problem
Existing oncolytic viruses face limitations in anti-tumor efficacy, safety concerns due to potential reversion to virulence, and challenges in delivering them to non-solid tumors and micrometastases.
Innovation Solution
A modified M1 virus with specific mutations at the NS3 protein's 358th site and E2 protein's 4th site, enhancing its anti-tumor spectrum and safety, and allowing intravenous administration for broader tumor treatment.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If wild-type M1 virus is used for oncolytic therapy, then the virus can infect and kill tumor cells, but the anti-tumor spectrum is limited and efficacy is low for certain cancer types
Solution Approach 1:
The patent applies parameter changes by modifying specific amino acid residues in the M1 virus genome (nucleotide positions 1433-1435 and 1520-1522) to alter the virus's biological properties. These genetic parameter modifications enable the virus to overcome limitations in anti-tumor spectrum and enhance efficacy across multiple cancer types including pancreatic cancer, nasopharyngeal carcinoma, prostate cancer, melanoma, glioma, cervical cancer, and lung cancer
2Object-affected harmful factors
If oncolytic viruses are modified and attenuated to improve safety, then the virus becomes less dangerous, but it may still become an escaping virus that rapidly infects healthy tissues
Solution Approach 1:
The patent applies the taking out principle by removing specific amino acid sequences from the M1 virus genome. Deletion of nucleotides 1433-1435 (encoding amino acids 478-479 of NS3 protein) and/or 1520-1522 (encoding amino acid 507 of E2 protein) extracts the virulence factors while maintaining oncolytic activity, preventing the virus from becoming an escaping virus that infects healthy tissues
Solution Approach 2:
The patent modifies viral parameters by changing specific nucleotide sequences to alter protein structure and function. The mutations in NS3 and E2 proteins change the virus's interaction with host cells, reducing toxicity to healthy tissues while preserving tumor-selective oncolytic activity
3Ease of operation
If oncolytic viruses are injected directly into tumor tissue, then the virus can target the lesion, but this method cannot treat non-solid tumors or micrometastases distributed throughout the body
Solution Approach 1:
The patent applies universality by modifying the M1 virus to enable systemically administered delivery that can treat multiple tumor types through a single treatment approach. The genetically engineered virus can be delivered via intravenous injection and effectively targets both solid tumors and non-solid tumors including hematological tumors, making the therapy universally applicable across different cancer types without requiring site-specific injection
Data Source
AI summary
Provided is an M1 virus. Further provided are a series of uses of said virus. The uses include, but are not limited to, viral vectors, anti-tumor agents, and pharmaceutical compositions. Said virus can effectively inhibit the growth of various tumor cells, and at the same time, has tumor targeting properties and is non-toxic to normal cells. Said virus can be administrated by means of intravenous injection, having operational convenience.