Researchers harness novel RNA-targeting CRISPR system

A team of researchers from the Broad Institute of MIT and Harvard, McGovern Institute for Brain Research at the Massachusetts Institute of Technology, the National Institutes of Health, and the Skolkovo Institute of Science and Technology has discovered and characterized two new types of RNA-targeting CRISPR systems, which utilize a new Cas enzyme, dubbed Cas13b. 

Cas13b is capable of targeting and degrading RNA, and its discovery, reported in Molecular Cell, is expected to open new avenues for RNA manipulation and accelerate progress to understand, treat, and prevent disease. This ability to target only RNA, which helps carry out genomic instructions, allows researchers to specifically manipulate RNA in a high-throughput manner—and manipulate gene function more broadly. The characterization of Cas13b has the potential to create a suite of RNA manipulation tools for studying a wide-range of biological processes.

“Beyond direct RNA cleavage, there are numerous RNA-binding applications,” said Aaron Smargon, graduate research assistant in the Zhang lab, who co-authored the study with colleagues Neena Pyzocha and David Cox. “Transcriptomic RNA engineering will open up new avenues of research in biology, particularly for complex dynamic systems such as those found in cancer, immunology, and neuroscience.”

The study, led by Broad core institute member Feng Zhang, employed a computational data-mining method to search diverse microbial genomes for CRISPR systems. Unlike previous bioinformatics approaches, Zhang and his team focused on systems lacking cas1, the most common gene related to CRISPR immunity, which enabled them to discover novel systems.

The newly characterized enzyme shares some of the features of Cas13a (formerly known as C2c2)—an RNA-targeting enzyme first characterized by the Broad and its colleagues in June 2016. Cas13b, like Cas13a, requires only a single guide RNA to specify the target and is also genetically encodable—meaning the necessary components can be synthesized as DNA for delivery into tissue and cells—and capable of targeting multiple RNA transcripts simultaneously.

But Cas13b possesses some unique features suggesting it evolved separately from Cas13a—and these features may make it more suitable for “fine-tuning” gene function, enable improved targeting, and provide opportunities for additional modes of RNA manipulation.  

“One goal of our lab is to develop widely accessible tools for researchers to better understand and treat human disease,” said Neena Pyzocha, co-first author. “Cas13b is the newest tool in the toolbox, and we're excited to see the advances it will support in the future.”