CRISPR-Cas Nuclease Guide RNA Targeting VZV Genomic DNA

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Solution Overview

Problem

Current therapeutic approaches fail to completely eradicate latent viruses such as Varicella Zoster Virus (VZV) from host cells, as they cannot selectively target and remove viral nucleic acid without interfering with host genetic material.

Innovation Solution

Development of compositions comprising a CRISPR-associated endonuclease and a guide RNA sequence that specifically target and cleave viral nucleic acid, using the CRISPR/Cas system to introduce targeted mutations or deletions in the viral genome without affecting host DNA.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current therapeutic approaches are used to treat VZV infection, then viral replication can be inhibited, but the virus cannot be completely eradicated from host cells

Engineering Contradiction:
Improveviral eradicationVSAvoidlatent virus persistence
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent extracts and removes the viral nucleic acid from host cells by using CRISPR/Cas system to specifically target and cleave VZV DNA sequences. The guide RNA directs the Cas nuclease to cut viral genomes, extracting the virus from the cellular environment and eliminating latent infection reservoirs that conventional therapies cannot remove.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The CRISPR/Cas system provides local quality by delivering nuclease activity specifically to viral nucleic acid sequences through guide RNA complementarity. The system distinguishes between viral and host DNA, applying cleavage only to VZV sequences while preserving host genomic integrity, thus achieving selective viral eradication without broad cellular damage.

Inventive Principle:
Principle #3Local quality

2Reliability

If nucleic acid cleavage is used to target viral DNA, then viral replication can be disrupted, but host genetic material may be affected

Engineering Contradiction:
Improveviral nucleic acid targetingVSAvoidhost DNA interference
Core Design Contradiction:
ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The guide RNA provides sequence-specific targeting that creates local quality differentiation between viral and host DNA. The CRISPR/Cas system recognizes and binds only to viral nucleic acid sequences complementary to the guide RNA, concentrating nuclease activity exclusively on VZV genomes while leaving host DNA unaffected.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The guide RNA acts as an intermediary molecule that mediates between the nuclease and viral DNA. It forms a complex with the Cas protein and directs it to specific viral sequences through base-pairing interactions, serving as a selective bridge that enables targeted cleavage without direct nuclease contact with host genetic material.

Inventive Principle:
Principle #24Intermediary (Mediator)

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

The CRISPR/Cas system effectively eradicates latent viruses by selectively targeting and disrupting viral genomic material, preventing viral replication and reactivation, thereby providing a potential cure for VZV infections.

Implementation Method 1

a guide RNA sequence complementary to a target sequence in VZV

Methodology Applied
Scientific EffectComplementary base pairing:

Implementation Method 2

nuclease is a Cas endonuclease and the sequence-specific binding module comprises a guide RNA

Methodology Applied
Scientific EffectCRISPR/Cas system:

Implementation Method 3

Causing the nuclease to cleave the viral nucleic acid

Methodology Applied
Scientific EffectEndonuclease cleavage:

Implementation Method 4

introduce targeted mutations or deletions in the viral genome

Methodology Applied
Scientific EffectGenomic disruption:

Data Source

PatentUS20230167425A1RNA guided eradication of varicella zoster virus
Publication Date: 2023.06.01 TEMPLE UNIV
  • US20230167425A1 patent drawing
  • US20230167425A1 patent drawing
  • US20230167425A1 patent drawing

AI summary

Compositions that specifically cleave target sequences in Herpesviridae, for example Varicella zoster virus (VZV) include nucleic acids encoding a Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) associated endonuclease and a guide RNA sequence complementary to a target sequence in VZV. These compositions are administered to a subject for treating an infection or at risk for contracting a VZV infection.