Recombinant Oncolytic Virus Expressing Basic Peptide for Tumor pH Modification
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Solution Overview
Problem
Current oncolytic viruses used to target cancer cells often cause systemic symptoms and have limitations in effectively modifying the tumor microenvironment to inhibit tumor growth.
Innovation Solution
A recombinant oncolytic virus with an inserted exogenous DNA sequence that expresses a basic peptide fragment, increasing the environmental pH in the host, is used to modify the tumor microenvironment and inhibit tumor growth, utilizing various oncolytic virus genomes such as herpes or Coxsackie viruses.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If wild-type oncolytic virus is used to infect and kill cancer cells, then anti-tumor effect is achieved, but systemic symptoms such as fever and chills occur
Solution Approach 1:
The patent extracts and removes the toxic components from the wild-type oncolytic virus through genetic modification, creating a recombinant virus that retains anti-tumor activity while eliminating systemic toxicity. The virus genome is engineered to delete or modify genes responsible for causing fever and chills.
Solution Approach 2:
The patent modifies the virus to exhibit local quality differences - it maintains high infectivity and cytotoxicity specifically against tumor cells while reducing or eliminating harmful effects on normal cells and systemic symptoms. This is achieved through tumor-selective replication mechanisms and targeted gene expression.
2Reliability
If conventional oncolytic virus is used, then tumor cells are killed, but the tumor microenvironment is not effectively modified
Solution Approach 1:
The patent creates a multi-functional oncolytic virus that simultaneously performs multiple functions: (1) direct tumor cell lysis through viral replication and cytolysis, (2) modification of tumor microenvironment through expression of therapeutic proteins (such as cytokines, immunomodulators, or pH-modifying peptides), and (3) potential induction of anti-tumor immunity. This universal approach addresses both tumor cells and their microenvironment.
Solution Approach 2:
The patent merges the functions of tumor cell killing and microenvironment modification into a single viral vector system. The recombinant virus carries multiple transgenes that are co-expressed in the tumor, combining oncolysis with microenvironmental conditioning in one therapeutic agent.
3Reliability
If basic peptide fragment is expressed to increase environmental pH, then tumor microenvironment is modified and anti-tumor effect is enhanced, but virus genome complexity increases
Solution Approach 1:
The patent segments the viral genome into functional modules, with the basic peptide fragment encoded as a separate transgene under the control of a specific promoter. This modular construction allows for systematic assembly and simplifies the process of adding or modifying functions without redesigning the entire viral genome.
Solution Approach 2:
The patent uses viral vectors and expression cassettes as intermediaries to carry and express the basic peptide fragment. These intermediary elements facilitate the integration of the peptide-encoding sequence into the viral genome and ensure its proper expression, thereby simplifying the overall process of genome modification.
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
The recombinant oncolytic virus effectively modifies the tumor microenvironment, providing a broad-spectrum anti-tumor effect with low toxicity and cumulative anti-tumor impact, suitable for treating solid tumors with minimal adverse effects.
Implementation Method 1
the exogenous DNA sequence being adapted to express a basic peptide fragment, to increase environmental pH in a host infected by the recombinant oncolytic virus
Data Source
AI summary
A recombinant oncolytic virus, a synthetic DNA sequence and applications of the virus are described. The recombinant oncolytic virus includes a genome and an exogenous DNA sequence inserted in the genome. The exogenous DNA sequence adapts to express a basic peptide fragment, to increase the environmental pH in a host infected by the recombinant oncolytic virus. More than 60% of amino acids in the basic peptide fragment are basic amino acids. The recombinant oncolytic virus and the synthetic DNA sequence of the disclosure are used to prepare an anti-tumor drug.