Programmable Inhibition and Detection of RNA Viruses Using Cas13

TLDR

Let's parse content. Combine: "The study aims to computationally identify Cas13 crRNA target sites across human-infecting ssRNA viruses and to develop CARVER, a platform that uses Cas13 to detect and destroy viral RNA." Mechanism: lines with [Mechanism] include first [Purpose, Mechanism] line, second [Purpose, Mechanism] line, and [Mechanism] line: "We further screen hundreds of crRNAs along the LCMV genome to evaluate how conservation and target RNA nucleotide content influence Cas13's antiviral activity." So mechanism: computational screening of crRNAs, experimental validation across viruses, and development of CARVER platform. Summarize: "The authors performed a genome-wide computational screen of Cas13 crRNAs across hundreds of ssRNA viruses, experimentally tested antiviral activity against LCMV, IAV, and VSV, and built the CARVER platform that couples Cas13 detection and cleavage." Findings: lines with [Findings] and [Findings, Other] include: "We experimentally demonstrate Cas13's potent activity against three distinct ssRNA viruses: LCMV; IAV; and VSV." and "Our results demonstrate that Cas13 can be harnessed to target a wide range of ssRNA viruses and CARVER's potential broad utility for rapid diagnostic and antiviral drug development." So findings: Cas13 shows potent antiviral activity against LCMV, IAV, VSV, and CARVER has broad utility for diagnostics and antiviral development. Other: lines with [Findings, Other] includes that sentence. Also maybe Graphical abstract line?

Abstract

Highlights•Thousands of potential Cas13 target sites are present in ssRNA viral genomes•Cas13 is a potent antiviral against three diverse ssRNA viruses in cell culture•Optimal Cas13 target sites and design criteria are identified via genome-wide screen•Companion Cas13-based diagnostics can be used to assess the effects of targetingSummaryThe CRISPR effector Cas13 could be an effective antiviral for single-stranded RNA (ssRNA) viruses because it programmably cleaves RNAs complementary to its CRISPR RNA (crRNA). Here, we computationally identify thousands of potential Cas13 crRNA target sites in hundreds of ssRNA viral species that can potentially infect humans. We experimentally demonstrate Cas13's potent activity against three distinct ssRNA viruses: lymphocytic choriomeningitis virus (LCMV); influenza A virus (IAV); and vesicular stomatitis virus (VSV). Combining this antiviral activity with Cas13-based diagnostics, we develop Cas13-assisted restriction of viral expression and readout (CARVER), an end-to-end platform that uses Cas13 to detect and destroy viral RNA. We further screen hundreds of crRNAs along the LCMV genome to evaluate how conservation and target RNA nucleotide content influence Cas13's antiviral activity. Our results demonstrate that Cas13 can be harnessed to target a wide range of ssRNA viruses and CARVER's potential broad utility for rapid diagnostic and antiviral drug development.Graphical abstract