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With a little detective work, CRISPR can say what that infection is

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Just ask SHERLOCK

Photo: Broad Institute of MIT and Harvard

CRISPR is already known for its power as a gene-editing tool that could one day transform how we fight cancer and other life-threatening diseases. But CRISPR’s potential is broader than that — and a new study using the technology has shown it can diagnose infections as well.

Researchers have created a version of CRISPR that can detect viruses like Zika and dengue, as well as other harmful bacteria, according to a study published in Science. The system, called SHERLOCK, could one day be a cheap and easy-to-use diagnostic tool.

CRISPR is based on a defense mechanism bacteria use to ward off viruses — cutting off bits of their DNA and pasting them elsewhere. Scientists have engineered that mechanism to reorder bits and pieces of the genetic code, and have used it to create unusually muscular beagles, for instance, and mosquitoes that don’t transmit malaria. But there are different types of CRISPR, with different types of molecular scissors. The gene-editing tool we often hear about is called CRISPR-Cas9. The CRISPR used in today’s study is called CRISPR-C2c2 (or CRISPR-Cas13a).

Instead of snipping DNA, this type of CRISPR largely aims at a different genetic building block — RNA, another of the major biological molecules found in all forms of life. Most of the time, RNA is used inside the body to help DNA build proteins. When C2c2 recognizes its RNA target, it does something interesting: it also cuts nearby RNAs that aren’t targeted, says study co-author James Collins, a bioengineering professor at MIT.

So scientists decided to engineer CRISPR-C2c2 into an easy-to-use diagnostic tool, called SHERLOCK. It works this way: the CRISPR system is reprogrammed to detect the genetic sequence of a specific virus or bacteria inside a person’s saliva, urine, blood, skin swab, or even stool sample. When CRISPR detects it, it also cuts a so-called “reporter RNA” that releases a fluorescent signal. So if blood is infected with the Zika virus, for example, scientists are able to see the signal and quickly diagnose a patient.

Today’s study builds on previous research published in Nature last year by a team of scientists at the University of California, Berkeley. That paper showed that the fluorescent signal process is possible with C2c2, Jennifer Doudna, a CRISPR pioneer and co-author of the Nature study, writes in an email to The Verge. Collins and his colleagues combined that process with a technique that boosts the sensitivity and accuracy with which C2c2 targets RNA. "They were able to really take this proof of concept to the next level in terms of sensitivity to something that could be used in a clinic or in the field to detect viruses or bacteria,” says Mitchell O'Connell, a postdoctoral fellow at Doudna’s lab and one of the lead authors of the Nature paper.

Today’s Science study shows that SHERLOCK is effective at identifying Zika and dengue virus, as well various bacterial strains like E. coli, Pseudomonas, and Klebsiella pneumoniae. These bacteria are all responsible for causing nasty, life-threatening infections. They also showed that the system can correctly identify genetic sequences associated with a cancer mutation. And the tests were cheap, at 61 cents an assay, the study says.

SHERLOCK has only been used in the lab so far. But because it’s so cheap, it shows promise for development into a handheld device that can diagnose infections. Think of it as a pregnancy test for Zika or Ebola. “We think it’s an affordable system” that can be used “for a broad range of applications,” Collins says.

Before that happens, however, a few things need to be figured out. The system, for example, requires parts of the RNA to be reproduced repeatedly so that the genetic sequence can be detected accurately. “This could be challenging to scale into a point-of-care application,” Doudna says. SHERLOCK also needs to be tweaked so that it can detect multiple viruses and bacteria in a sample at the same time, Collins says. And “making it robust to false positives (think contamination) and false negatives (think user error) will require substantially more work,” Jamie Cate, a professor of biochemistry, biophysics, and structural biology at UC Berkeley, who did not take part in the study, writes in an email to The Verge.

But as medicine tries to steer toward more and more targeted therapies, it’s more important than ever to have very precise diagnostic tools, Collins says. “As we advance our ability to treat diseases, we need to continually enhance our ability to rapidly and inexpensively diagnose” those diseases, Collins says. That means SHERLOCK is on-trend: it can identify exactly what a patient has, and in the case of cancer, it can identify which treatment is most likely to generate the best response.

So by all means, get excited about de-extinction and the other possibilities for CRISPR — just remember that SHERLOCK has the potential to be the type of CRISPR that will make a dramatic change to your medical care.