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A comprehensive analysis and resource to use CRISPR-Cas13 for broad-spectrum targeting of RNA viruses

Xueqiu Lin1, Yanxia Liu1, Augustine Chemparathy1,2

  • 1Department of Bioengineering, Stanford University, Stanford, CA 94305, USA.

Cell Reports. Medicine
|March 29, 2021
PubMed

Insights

A new bioinformatic analysis shows that the prophylactic antiviral CRISPR in human cells (PAC-MAN) system can target over 90% of human infectious RNA viruses. This CRISPR-based antiviral strategy shows promise for broad-spectrum RNA virus targeting.

Area of Science:

  • Molecular Biology
  • Virology
  • Bioinformatics

Background:

  • The COVID-19 pandemic highlights the urgent need for broad-spectrum antiviral strategies.
  • The CRISPR-Cas13 system, PAC-MAN, has previously shown potential against SARS-CoV-2 and influenza A virus.

Purpose of the Study:

  • To computationally assess the potential of PAC-MAN for targeting a wide range of human and livestock RNA viruses.
  • To identify a minimal set of CRISPR RNAs (crRNAs) for broad-spectrum viral targeting.
  • To develop a community resource for CRISPR-Cas13 antiviral applications.

Main Methods:

  • Extensive in silico analysis of PAC-MAN's targeting capabilities across diverse RNA viruses.
  • Bioinformatic prediction of crRNA efficiency, specificity, and coverage.
  • Development of an online resource for CRISPR-Cas13 antiviral research.

Main Results:

  • A minimal set of 14 crRNAs can target over 90% of human-infectious viruses across 10 RNA virus families.
  • A smaller set of 5 crRNAs is predicted to target new SARS-CoV-2 variants with high accuracy.
  • An online resource (crispr-pacman.stanford.edu) is now available for researchers.

Conclusions:

  • CRISPR-Cas13, via the PAC-MAN system, offers a promising bioinformatic resource for broad-spectrum RNA virus targeting.
  • This approach facilitates the development of novel CRISPR-based antiviral therapies.
  • The identified crRNAs and online tool can accelerate research into combating diverse viral threats.
Keywords:
COVID-19CRISPRCas13PAC-MANRNA virusSARS-CoV-2antiviralinfectious disease

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