Vaccinia Virus Vectors With Fused Complement Regulators
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Solution Overview
Problem
Existing oncolytic viruses, such as vaccinia, are rapidly recognized and eliminated by the immune system before they can effectively infect target cancer cells, limiting their therapeutic potential for visceral or disseminated tumors.
Innovation Solution
Engineered vaccinia viruses with complement regulatory proteins fused to envelope proteins, allowing them to evade the immune response and maintain viability in vivo, enabling prolonged exposure and infection of distal tumor cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If vaccinia virus is administered systemically, then it can reach distal tumor cells, but it is rapidly inactivated by the immune system
Solution Approach 1:
The patent introduces complement regulatory proteins (CD55, CD59, CD46, CR1) as intermediary molecules fused to the viral envelope proteins. These intermediary proteins mediate the interaction between the virus and the complement system, specifically inhibiting complement activation and providing protection against immune-mediated virus inactivation, thereby enabling prolonged virus viability in the bloodstream
Solution Approach 2:
The patent creates composite viral envelope structures by fusing complement regulatory proteins with viral envelope proteins (such as A13 and A27). This composite approach combines the viral envelope components with protective immune-modulating proteins, resulting in a hybrid structure that maintains viral infectivity while providing enhanced resistance to complement-mediated destruction
2Reliability
If complement regulatory proteins are fused to envelope proteins, then immune evasion is enhanced, but viral structure complexity increases
Solution Approach 1:
The patent merges complement regulatory protein functions directly into the viral envelope structure through fusion proteins. Instead of adding separate protective molecules, the immune-evasion function is integrated into the existing envelope proteins (A13, A27), combining structural and protective functions into a single unified component
Data Source
AI summary
Disclosed herein are polynucleotides encoding fusion proteins, the fusion proteins comprising a vaccinia virus envelope protein, such as A13 or part thereof and at least one complement regulatory protein, such as CD35, CD55, CD59, CD46, CR1, Factor H, VCP, MOPICE, SPICE and CCPH, or a functional fragment thereof. Modified vaccinia virus vectors and vaccinia virus virions are also disclosed, as are therapeutic uses and methods for treatment of cancers and/or proliferative diseases or disorders.