COVID-19 one year later: a retrospect of CRISPR-Cas system in combating COVID-19

Abstract

Coronavirus disease 2019 (COVID-19), an infectious disease caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has posed a persistent global threat. The transmission of SARS-CoV-2 is wide and swift. Rapid detection of the viral RNA and effective therapy are imperative to prevent the worldwide spread of the new infectious disease. Clustered Regularly-Interspaced Short Palindromic Repeats (CRISPR)- CRISPR-associated protein (Cas) system is an RNA-directed adaptive immune system, and it has been transformed into a gene editing tool. Applications of CRISPR-Cas system involves in many fields, such as human gene therapy, drug discovery and disease diagnosis. Under the background of COVID-19 pandemic, CRISPR-Cas system shows hidden capacity to fight the emergency in many aspects. This review will focus on the role of gene editing in COVID-19 diagnosis and treatment. We will describe the potential use of CRISPR-Cas-based system in combating COVID-19, from diagnosis to treatment. Furthermore, the limitation and perspectives of this novel technology are also evaluated.

Keywords: COVID-19; CRISPR-Cas; SARS-CoV-2; diagnosis; gene editing; mechanism research; therapeutics.

Figure 1

Schematics for SARS-CoV-2 genome and the natural defense mechanism of CRISPR system. (A) The skeleton diagram of SARS-CoV-2 genome. Light purple represents ORF1a and ORF1b, which encode non-structural proteins. Dark purple represents four structural protein-encoding genes. Green represents nine accessory protein-encoding genes. (B) A brief description of CRISPR-Cas system mechanism in defending foreign genetic material.

Figure 2

Schematics for CRISPR-Cas based applications in COVID-19. The mentioned contents were summarized in this figure. In the top of the picture, a cardinal principle of CRISPR-based diagnosis was shown. Researchers extracted patient sample RNA from nasopharyngeal or oropharyngeal swabs, and transformed RNA into cDNA with the process of reverse transcription. Then amplified virus cDNA, and use Cas protein targets predefined coronavirus sequences. The collateral cleavage of ssDNA probe confirmed detection of the virus. In the middle of the picture, the mechanism of therapeutics was depicted. Genome viral mRNA was degradation after CRISPR-Cas system cleavage, and the viral gene expression have also been inhibited. In the bottom of the picture, potential utilization of CRISPR in COVID-19 mechanism research was exhibited.