Modified B5R Vaccinia Vector for Higher EEV Output in Solid Tumors
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current oncolytic vaccinia virus therapies are ineffective in treating solid tumors due to low extracellular enveloped virus (EEV) production and limited immune activation, despite their potential as potent cancer therapeutics.
Innovation Solution
A vaccinia virus vector with a deleted B5R gene (B5R SCR1− SCR2− SCR3− SCR4−) is inserted into the TK gene, enhancing EEV production and immune activation by incorporating a nucleic acid sequence encoding a partial B5R gene, along with optional heterologous proteins for targeted cancer therapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If the complete B5R gene is present in vaccinia virus, then the virus can form extracellular enveloped virus (EEV), but the EEV production is insufficient to effectively treat solid tumors
Solution Approach 1:
The patent applies local quality by modifying only specific domains (SCR1-4) of the B5R gene while preserving other functional regions. This localized modification approach allows the virus to maintain essential EEV formation capabilities while enhancing tumor-targeting properties and immune activation, thereby improving treatment efficacy without completely redesigning the viral structure.
Solution Approach 2:
The patent changes the structural parameters of the B5R gene by deleting specific consensus repeat domains (SCR1-4). This parameter change alters the viral envelope properties, enabling enhanced EEV production and improved tumor penetration while maintaining the ability to form infectious particles, thus resolving the contradiction between productivity and reliability.
2Productivity
If the B5R gene is completely deleted to increase EEV production, then EEV formation increases, but the virus loses ability to effectively target and kill cancer cells
Solution Approach 1:
The patent extracts only the specific SCR1-4 domains from the B5R gene for deletion, rather than removing the entire gene. This selective extraction allows the virus to gain enhanced EEV production capabilities while retaining the essential functions needed for cancer cell targeting and killing, thus resolving the contradiction between increased productivity and maintained harmful factor generation.
Solution Approach 2:
The patent segments the B5R gene into functional domains and selectively modifies only the SCR1-4 regions. This segmentation approach enables precise control over viral properties, allowing enhanced EEV formation while preserving the tumor-killing functionality encoded in other parts of the B5R gene or compensatory viral mechanisms.
3Productivity
If conventional oncolytic viruses are used, then they can replicate in cancer cells, but they are ineffective in hypoxic microenvironment of solid tumors
Solution Approach 1:
The patent changes the viral envelope parameters by modifying the B5R gene structure, which alters the virus's interaction with hypoxic environments. This parameter change enables the virus to maintain replication productivity in the hypoxic microenvironment of solid tumors while preserving its ability to kill cancer cells, resolving the contradiction between replication and efficacy.
Data Source
AI summary
The present invention relates to a vaccinia virus vector comprising a nucleic acid sequence encoding a SCR1−, SCR2−, SCR3−, and SCR4− domain deleted B5R gene (B5R SCR1− SCR2− SCR3− SCR4−) inserted into the TK gene of the vaccinia virus. The invention also relates to compositions comprising the vaccinia virus vector, methods of treatment using the compositions, medical uses of the compositions and kits comprising the vaccinia virus vector. The invention also relates to a nucleic acid sequence encoding a SCR1−, SCR2−, SCR3−, and SCR4− domain deleted B5R gene (B5R SCR1− SCR2− SCR3− SCR4−) of vaccinia virus.