ICP4/ICP47-Deleted HSV-1 Vectors for Sustained Therapeutic Expression
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Solution Overview
Problem
Existing viral vectors for delivering therapeutics to treat cancer exhibit insufficient persistence, non-specific inflammation, and tissue damage, limiting their effectiveness in targeting tumor cells.
Innovation Solution
HSV-1 vectors with alterations to prevent expression of ICP4 and ICP47 proteins, which enhance immunogenicity and persistence, allowing for sustained therapeutic payload delivery and immune activation, and include specific therapeutic polypeptides to target tumor stroma, support immune cell survival, and induce tertiary lymphoid structures.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of stationary object
If existing viral vectors are used to deliver therapeutics to treat cancer, then therapeutic delivery to cells is achieved, but insufficient persistence in target cells prevents sufficient expression of therapeutics
Solution Approach 1:
The patent modifies the viral vector by deleting specific genes (ICP4 and ICP47) that regulate viral replication and gene expression. This parameter change in the viral genome results in reduced viral replication while enhancing persistence of the vector and its therapeutic payload in target cells, thereby resolving the contradiction between persistence and therapeutic expression.
2Reliability
If existing viral vectors are used to deliver therapeutics, then therapeutic delivery is achieved, but non-specific inflammation and tissue damage make delivery unsafe
Solution Approach 1:
The patent extracts and removes specific viral genes (ICP4 and ICP47) that are responsible for causing non-specific inflammation and tissue damage. By taking out these harmful genetic elements while retaining the therapeutic delivery capability, the vector achieves safe delivery without compromising its therapeutic function.
3Duration of action of moving object
If HSV-1 vectors with ICP4 and ICP47 deletions are used, then reduced replicative capacity and oncolytic activity are achieved, but extended period of payload expression requires careful control
Solution Approach 1:
The patent segments the viral vector design into distinct functional components: the deleted ICP4 and ICP47 genes that control replication, the therapeutic payload genes that provide treatment effect, and the remaining viral genes that maintain vector functionality. This segmentation allows independent optimization of each component, achieving extended payload expression while managing overall vector complexity through modular design.
Data Source
AI summary
The invention relates generally to replication defective HSV-1 vectors, and, more particularly, the invention relates to replication defective HSV-1 vectors comprising an alteration (such as a gene deletion) that prevents expression of one or more infected cell polypeptide 4 (ICP4) and infected cell polypeptide 47 (ICP47) proteins, and their use to deliver one or more genes encoding transgenic proteins that stimulate immune destruction of tumors.