RNA plays important and diverse roles in biology, but molecular tools to manipulate and measure RNA are limited. We demonstrate that RNA-targeting CRISPR effector Cas13 and novel RNA targeting effectors, such as the newly described CRISPR Cas7-11, can be engineered for RNA diagnostics and mammalian cell RNA knockdown, binding, and editing. We demonstrate diagnostic applications of Cas13 for rapid and sensitive COVID-19 diagnostics. We also show Cas13 and Cas7-11 can be heterologously expressed in mammalian and plant cells for targeted knockdown of either reporter or endogenous transcripts, targeted RNA binding for transcript imaging, and programmable RNA editing. We develop engineered RNA editing tools for A-to-I and C-to-U base editing and show applications of these tools for therapeutics. Our results establish CRISPR-Cas13 and other novel effectors as a flexible platform for RNA targeting with wide applicability for studying RNA or therapeutics.

Learning Objectives:

1. Explain use cases and differentiating characteristics of CRISPR diagnostics, including STOPCovid.

2. Identify applications of novel RNA-targeting CRISPR systems.

3. Distinguish between CRISPR effectors, including Cas13 and Cas7-11, their effects on mammalian cells, and their potential therapeutic uses.