CRISPR/Cas Genome Editing for HSV Gene Knockout
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Solution Overview
Problem
Current treatments for herpes simplex virus (HSV) infections, particularly ocular infections, lack effective curative or preventative measures, with existing antiviral therapies only managing symptoms and vaccines showing limited efficacy.
Innovation Solution
The use of CRISPR/Cas-based genome editing systems to target and alter the RS1, RL2, and LAT genes of HSV, either by knocking out or knocking down their expression, thereby reducing viral infectivity and replication.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antiviral therapies are used to manage HSV symptoms, then symptomatic relief is achieved, but curative or preventative effect is not obtained
Solution Approach 1:
The CRISPR/Cas system extracts and eliminates specific viral genes (RS1, RL2, LAT) from the HSV genome through targeted DNA cleavage. The guide RNA directs the Cas nuclease to precise viral gene sequences, cutting the DNA and preventing viral replication, thereby achieving curative effectiveness by removing the harmful viral genetic material rather than just managing symptoms
Solution Approach 2:
The patent replaces the mechanical/chemical approach of antiviral drugs (which inhibit viral processes) with a genetic editing system. The CRISPR/Cas mechanism uses programmed RNA-DNA hybridization and enzymatic cleavage to directly modify the viral genome, substituting symptomatic management with precise genetic intervention that can prevent and cure infections
2Reliability
If vaccines are administered to prevent HSV infection, then some protection is provided, but efficacy is limited
Solution Approach 1:
The CRISPR/Cas system performs preliminary action by preemptively targeting and disabling viral genes before the virus can establish latent infection or reactivate. By introducing the editing system that recognizes and cuts viral DNA sequences, the patent prevents the virus from establishing permanent latent infection, offering robust preventative protection against both primary and recurrent infections
Solution Approach 2:
The invention changes the fundamental parameter of viral genome integrity by introducing double-strand breaks at specific viral gene locations. This genetic modification alters the viral replication cycle from successful latency establishment to failed infection, providing adaptable protection against different HSV strains and reactivation events
3Productivity
If CRISPR/Cas system targets viral genes, then viral replication is reduced, but treatment complexity increases
Solution Approach 1:
The CRISPR/Cas system segments the complex task of antiviral therapy into modular components: guide RNA molecules that can be independently designed for each viral target, Cas nuclease enzymes that perform the cutting function, and delivery vectors that transport the system to infected cells. This segmentation allows the complex genome editing function to be achieved through coordinated simple components, reducing overall system complexity while maintaining high viral replication reduction efficacy
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
This approach potentially provides a curative or preventative solution for HSV infections by significantly reducing viral replication and infectivity, offering a more effective treatment than existing therapies.
Implementation Method 1
The use of CRISPR/Cas-based genome editing systems to target and alter the RS1, RL2, and LAT genes of HSV, either by knocking out or knocking down their expression
Data Source
AI summary
CRISPR/CAS-related systems, compositions and methods for editing RS1, RL2, and/or LAT genes in human cells are described, as are cells and compositions including cells edited according to the same.