Herpes Simplex Virus Strain HL-1 Oncolytic Therapy
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Solution Overview
Problem
Current herpes simplex virus (HSV) strains used for gene therapy have limitations in infecting and replicating within tumor cells, and existing oncolytic viruses lack enhanced antitumor immune response and transfection capabilities.
Innovation Solution
A novel HSV-1 isolate, strain HL-1, with enhanced replication and killing abilities within tumor cells, and a non-replicating recombinant herpes virus with improved transfection and gene expression capabilities, derived from a strain with specific gene knockouts or mutations, such as ICP34.5 and ICP47, are developed for improved oncolytic and gene therapy applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If conventional HSV-1 strains are used for gene therapy, then the virus can infect and replicate within tumor cells, but the replication and killing abilities are insufficient
Solution Approach 1:
The patent modifies viral parameters by knocking out specific genes (ICP34.5, ICP47, US3, ICP0, UL56) to change the virus's biological properties. This genetic modification transforms the virus into an oncolytic form that selectively replicates in and kills tumor cells while sparing normal cells, thereby simultaneously improving both replication ability and killing ability through parameter changes in the viral genome
2Quantity of substance
If HSV-1 is used as a gene therapy vector, then it can carry large genomes and multiple exogenous genes, but the transfection and gene expression capabilities are limited
Solution Approach 1:
The patent extracts or removes specific genes (ICP34.5, ICP47, US3, ICP0, UL56) from the HSV-1 genome to create a modified virus vector. This extraction process eliminates genes that limit transfection efficiency and gene expression, thereby improving the vector's ability to deliver and express therapeutic genes while maintaining its large genome capacity
3Object-generated harmful factors
If oncolytic viruses are used to kill tumor cells, then antitumor effect is achieved, but enhanced antitumor immune response is lacking
Solution Approach 1:
The patent converts the harmful viral infection into a beneficial therapeutic effect by designing an oncolytic virus that selectively infects and kills tumor cells. The viral replication and cell lysis release tumor antigens that stimulate the immune system, transforming the harmful viral action into a beneficial immunotherapeutic effect that enhances antitumor immune response
Data Source
AI summary
Provided are a new herpes simplex virus type I, a genetically modified herpes simplex virus, a composition containing the virus, a host cell and a cell culture, and the use of the virus in the treatment of diseases.