Using a New CRISPR Effector to Edit RNA

June 2, 2016
Randi Hernandez

Randi Hernandez was science editor at Pharmaceutical Technology from September 2014 to May 2017.

As the battle for ownership over the use of CRISPR to edit DNA heats up, some of the CRISPR pioneers refocus their efforts to demonstrate the technology’s applications for editing RNA.

A naturally occurring CRISPR (clustered regularly interspaced short palindromic repeats) system that specifically can be used to modify the RNA of an organism is the newest development in the technology’s evolution. A new study, published on June 2, 2016 in Science, identifies C2c2, a bacterial protein that can be used as a tool to cleave single-stranded RNA sequences at desired locations. As an RNA-guided RNAse, C2c2 can be harnessed to defend against viral intruders and turn off gene expression of certain conditions, according to researchers.

A new approach to RNA interference
Typically, gene silencing is a gene expression manipulation performed by small interfering RNA (siRNA), but the study researchers attest that the C2c2 complex is even more efficient when it comes to editing RNA. Specifically, C2c2 can be used to add to or delete information from existing RNA sequences, and can also be used to tag RNA to learn more information about the function of certain sequences. In addition, C2c2 can be programmed to knock out certain messenger RNA (mRNA), disrupting the DNA-->mRNA-->protein transcription process. C2c2 requires only a single RNA to function, and is “genetically encodable,” the researchers said in a Broad Institute/Harvard press release accompanying the study. As an RNA-targeting immune system mechanism, they say C2c2 is a promising tool for future RNA manipulation.

The authors concluded that the CRISPR-C2c2 complex is probably not the only system that can be programmed to alter RNA sequence, and other, patentable editing tools may be on the horizon. They wrote, “It is likely that other, broadly analogous Class 2 RNA-targeting immune systems exist, and further characterization of the diverse members of Class 2 systems will provide a deeper understanding of bacterial immunity and provide a rich starting point for the development of programmable molecular tools for in vivo RNA manipulation.”

Although the research on CRISPR-C2c2 was conducted by various teams at MIT, the Broad Institute, Harvard University, the National Institutes of Health, Rutgers University-New Brunswick, and the Skolkovo Institute of Science and Technology, the Broad Institute’s Feng Zhang is at the helm of the research and serves as one of the paper’s senior authors. Zhang is notorious for being one of the founders of the CRISPR-Cas9 complex and its applications for editing DNA, however, there is currently an ongoing legal battle between the Broad Institute and the University of California (involving work by researcher Jennifer Doudna and by French researcher Emmanuelle Charpentier) for the patent rights to the technology.

Sources: Science, The Broad Institute/Harvard