Abstract 1023 CRISPR-based detection and editing of RNA

In bacteria and archaea, CRISPR systems "diagnose" infections using diverse RNA-guided proteins. Complementary base pairing between the CRISPR RNA-guide and the target nucleic acid, drives conformational changes that activate the nuclease for cleavage of the invading target, which provides sequence-specific protection from infection. While most CRISPR systems target DNA cleavage, some CRISPR systems uniquely target RNA. In this presentation, I will explain how the SARS-CoV-2 pandemic unexpectedly changed the course of our research. Initially, our work on SARS-CoV-2 was an outreach effort designed to help the local hospital established a testing center. However, moving from the lab and into the hospital, we experienced first-hand the overwhelming demand and impractical delays that are intrinsic to qPCR. This experience led us to the realization that CRISPR systems naturally function as molecular diagnostics in bacterial cells, and we set out to repurpose type III CRISPR systems for applications that enable amplification-free RNA diagnostics. In addition to detecting RNA, type III CRISPR systems also cleave the RNA target. Harnessing the RNA targeting capabilities of this system, we have developed new RNA editing technologies that enables sequence-specific changes to the human transcriptome. Collectively, we imagine that the find (diagnostic) and fix (RNA editing) functions of RNA targeting CRISPR systems can be harnessed for new applications that directly address unmet needs in healthcare. Research supported by the National Institutes of Health (1K99AI171893, 1K99GM147842, P20GM103474, NSF 1828765, U24 GM129539, and R35GM134867), Montana State University Agricultural Experimental Station (USDA NIFA), the M.J. Murdock Charitable Trust and the Simons Foundation.