Using CRISPR to fight epidemics

April 30, 2018

The CRISPR-Cas9 system has received global attention as it revolutionizes gene editing, and justifiably so. But DNA-editing isn’t the only trick up CRISPR’s sleeve – as Hertz Fellow Cameron Myhrvold knows well. Myhrvold, a postdoctoral scholar in the Sabeti lab at the Broad Institute of MIT and Harvard, is working with colleagues at Broad and around the world to turn a slightly different system, called CRISPR-Cas13, into a sensitive tool for detecting viral infection in the midst of outbreaks.

CRISPR sequences are just short sequences of RNA that can guide proteins to a particular DNA or RNA sequence. Cas9 (“Cas” stands for “CRISPR-associated”) acts like DNA scissors, slicing DNA where the CRISPR sequence guides it. Cas13, a cousin of Cas9, targets RNA instead.

Since many viruses, including those behind headline-grabbing epidemics like Dengue and Zika, use RNA for their genomes, researchers at the Broad institute – including Myhrvold – have been working to use the CRISPR-Cas13 system as a diagnostic test, detecting viral genes in samples of bodily fluids. The system, known as SHERLOCK, is sensitive enough to particular sequences that it is able not only to distinguish between similar viruses like Dengue and Zika, but also to distinguish between different strains of the viruses, finding mutations associated with drug resistance, geographic origin, or disease progression.

But the original SHERLOCK technique required extensive processing to extract the RNA from the bodily fluids – processing that couldn’t be performed without an expensive lab and trained technicians. So Myhrvold co-first author Catherine Freije decided to simplify the process, looking for the simplest way possible to make the viral RNA detectable to the test.

"It's a minimalist approach to the extraction," said Myhrvold. They found that only two steps were needed to prepare the samples – incubating them for 5-20 minutes with a common lab reagent to deactivate RNA-destroying enzymes typically present in our blood, and then heating them to destroy the virus particles and release the DNA. Their technique – Field-deployable viral diagnostics using CRISPR-Cas13 – was published this month in Science.

Myhrvold credits his time as a Hertz Fellow at Harvard with giving him the intuition to think about viruses as something to manipulate and engineer with simple methods. "A lot of the things I was trying to build in grad school were synthetic structures that were analogous to viruses, I've now shifted to studying viruses themselves. It's been great to come to a lab that studies viruses and take a design, testing, and engineering approach to things."

"We're actively working to expand the viruses we can detect,” said Myhrvold, “and working with our collaborators in South and Central America and West Africa to think of new ways to deploy the technology. There's still so much to learn here. It makes you wonder what the next couple years are going to look like."

You can see a video of Myhrvold and Freije explaining their research on the Broad Institute’s website, or read more from the Broad Institute’s press release.