Assessing the capacity of CRISPR systems as anti-viral therapies against SARS-CoV-2 variants of concerns

Abstract

Throughout the pandemic, COVID-19 has evolved into a disease of multiplicity; the rapid emergence of SARS-CoV-2 variants of concerns (VOCs) have revealed the necessity of broad-ranged, anti-viral treatments as a potential pandemic countermeasure. CRISPR systems are being explored as a promising venture to solve this issue. Current research on CRISPR anti-viral research has utilized the suitability of the CRISPR effector Cas13 due to the large amounts of potential Cas13 target sites on the SARS-CoV-2 genome as well as its ability to specifically cleave RNAs. Using bioinformatics pipelines, a wide variety of crRNAs can be generated and pooled to easily target a wide range of viral RNA sequences. Moreover, proof-of-concepts such as Cas13-assisted restriction of viral expression and readout (CARVER), and Prophylactic Antiviral CRISPR in huMAN cells (PAC-MAN) promote the feasibility and practicality of this idea. Despite this, the development of CRISPR systems as an anti-viral is still in its infancy, and many limitations must be first overcome before they can reach the clinical stage. This article will strive to objectively assess 1) the mechanisms of the antiviral CRISPR platforms and their potential as a pandemic countermeasure and 2) current limitations plaguing CRISPR Cas13 anti-viral development and a few possible solutions. It is important to understand the potential of CRISPR and how it could benefit Sars-CoV-2 research in ways that are lacking in available/traditional antiviral therapies. Moreover, employing these CRISPR systems would require the creation of novel solutions for overcoming the current obstacles against clinical testing. By further understanding the modularity of CRISPR systems, additional forays into countermeasures can be explored against not only the rapidly evolving strains of Sars-CoV-2, but any RNA virus.