Meanwhile, Back At The Ranch - Nerds Done Nerded Up An RNA Editing CRISPR CAS-7-11

phys.org  |  Researchers at MIT's McGovern Institute for Brain Research have discovered a bacterial enzyme that they say could expand scientists' CRISPR toolkit, making it easy to cut and edit RNA with the kind of precision that, until now, has only been available for DNA editing. The enzyme, called Cas7-11, modifies RNA targets without harming cells, suggesting that in addition to being a valuable research tool, it provides a fertile platform for therapeutic applications.

"This new enzyme is like the Cas9 of RNA," says McGovern Fellow Omar Abudayyeh, referring to the DNA-cutting CRISPR enzyme that has revolutionized modern biology by making DNA editing fast, inexpensive, and exact. "It creates two precise cuts and doesn't destroy the cell in the process, like other enzymes," he adds.

Up until now, only one other family of RNA-targeting enzymes, Cas13, has extensively been developed for RNA targeting applications. However, when Cas13 recognizes its target, it shreds any RNAs in the cell, destroying the cell along the way. Like Cas9, Cas7-11 is part of a programmable system; it can be directed at specific RNA targets using a CRISPR guide. Abudayyeh, McGovern Fellow Jonathan Gootenberg, and their colleagues discovered Cas7-11 through a deep exploration of the CRISPR systems found in the microbial world. Their findings were recently reported in the journal Nature.

Exploring natural diversity

Like other CRISPR proteins, Cas7-11 is used by bacteria as a defense mechanism against viruses. After encountering a new virus, bacteria that employ the CRISPR system keep a record of the infection in the form of a small snippet of the pathogen's genetic material. Should that virus reappear, the CRISPR system is activated, guided by a small piece of RNA to destroy the viral genome and eliminate the infection.

These ancient immune systems are widespread and diverse, with different bacteria deploying different proteins to counter their viral invaders.

"Some target DNA, some target RNA. Some are very efficient in cleaving the target but have some toxicity, and others do not. They introduce different types of cuts, they can differ in specificity—and so on," says Eugene Koonin, an evolutionary biologist at the National Center for Biotechnology Information.

Abudayyeh, Gootenberg, and Koonin have been scouring genome sequences to learn about the natural diversity of CRISPR systems—and to mine them for potential tools. The idea, Abudayyeh says, is to take advantage of the work that evolution has already done in engineering protein machines.

"We don't know what we'll find," Abudayyeh says, "but let's just explore and see what's out there."