CRISPR-Cas13d Viral Genome Targeting for Broad-Spectrum Antiviral Therapy
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Solution Overview
Problem
Current methods are inadequate for effectively detecting, mutating, and degrading viral genomes to treat or prevent viral infections, particularly for unpredictable and highly contagious viruses like coronaviruses and influenza viruses, where existing vaccines or treatments may not be effective.
Innovation Solution
A system comprising heterologous polypeptides or nucleic acid molecules that specifically bind to target viral genes, such as those encoding RNA-dependent RNA polymerase and nucleocapsid protein, to reduce their expression and activity, using CRISPR/Cas proteins like Cas13d to target and cleave viral RNA, and a combination of therapeutic agents to enhance infection reduction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing vaccines or treatments are used, then they may be effective against known viruses, but they become ineffective when virus strains evolve and transfer to humans from animal hosts
Solution Approach 1:
The patent employs a universal CRISPR-Cas13d system that can target multiple viral families (coronaviruses, influenza viruses, and other RNA viruses) through a single platform. By designing guide RNAs that complementary bind to conserved regions across different viral strains, the system achieves broad-spectrum antiviral activity, making it adaptable to evolving virus strains while maintaining reliable effectiveness.
2Productivity
If CRISPR/Cas13d system is used to target and cleave viral RNA, then viral infection is significantly reduced, but the system requires specific binding to target viral genes which limits broad applicability
Solution Approach 1:
The patent segments the viral genome into multiple targetable regions by designing multiple guide RNAs that bind to different conserved sequences across viral families. This segmentation allows the CRISPR-Cas13d system to target specific viral genes with high precision while maintaining the ability to adapt to different viral strains by simply changing the guide RNA sequences, thus achieving both high productivity and broad adaptability.
3Reliability
If multiple heterologous nucleic acid molecules are used to target different viral genes, then expression or activity of target viral genes is reduced, but the complexity of the system increases
Solution Approach 1:
The patent merges multiple antiviral functions into a single CRISPR-Cas13d system by co-delivering the Cas13d protein and multiple guide RNAs as a unified therapeutic complex. This merging approach allows simultaneous targeting of multiple viral genes (such as RdRP and N-protein) through a single administered system, reducing the need for multiple separate therapeutic agents while maintaining reliable gene expression reduction.
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 system significantly reduces viral infection by up to 85% across various coronavirus strains and 70% for influenza viruses, demonstrating a broad-spectrum antiviral efficacy by targeting multiple viral families with high specificity and efficiency.
Implementation Method 1
at least the gene regulating moiety or the one or more heterologous nucleic acid molecules are configured to specifically bind one or more target viral genes
Implementation Method 2
using CRISPR/Cas proteins like Cas13d to target and cleave viral RNA
Data Source
AI summary
Described herein are systems for targeting viral genomes. Also described herein are methods for targeting viral genomes utilizing the systems described in the instant disclosure. In some cases, systems and methods disclosed herein can be used to treat viral infections. In preferred embodiments, the systems utilise a CRISPR/Cas13d complex to target the genome of an RNA virus such as coronavirus or influenza virus.