Development of a Rapid and Sensitive CasRx-Based Diagnostic Assay for SARS-CoV-2

ACS Sens. 2021 Nov 26;6(11):3957-3966. doi: 10.1021/acssensors.1c01088. Epub 2021 Oct 29.

Abstract

The development of an extensive toolkit for potential point-of-care diagnostics that is expeditiously adaptable to new emerging pathogens is of critical public health importance. Recently, a number of novel CRISPR-based diagnostics have been developed to detect SARS-CoV-2. Herein, we outline the development of an alternative CRISPR nucleic acid diagnostic utilizing a Cas13d ribonuclease derived from Ruminococcus flavefaciens XPD3002 (CasRx) to detect SARS-CoV-2, an approach we term SENSR (sensitive enzymatic nucleic acid sequence reporter) that can detect attomolar concentrations of SARS-CoV-2. We demonstrate 100% sensitivity in patient-derived samples by lateral flow and fluorescence readout with a detection limit of 45 copy/μL. This technology expands the available nucleic acid diagnostic toolkit, which can be adapted to combat future pandemics.

Keywords: COVID-19; CRISPR; Cas13d; isothermal; nucleic acid diagnostic.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19*
  • Humans
  • Nucleic Acid Amplification Techniques
  • RNA, Viral
  • Ruminococcus
  • SARS-CoV-2*

Substances

  • RNA, Viral

Supplementary concepts

  • Ruminococcus flavefaciens