The CRISPR diagnostics era is here

ZikaTest_Paper-based-results-002-1024x576Elementary dear Watson, we should have expected that. The CRISPR wave is hitting diagnostics, with a new high sensitivity detection platform named after Arthur Conan Doyle’s popular detective. The acronym SHERLOCK stands for “Specific High Sensitivity Enzymatic Reporter UnLOCKing”. While the technique is used in thousands of labs to turn genes on and off, CRISPR embarks also on epidemiology and learns how to identify nucleic acids from viral and bacterial pathogens to diagnose infections. The paper published in Science by James Collins, Feng Zhang and colleagues heralds a new generation of low cost diagnostic tests with single-base specificity, easy to use even when oubreaks occur in remote areas.

The classic way to use CRISPR is to seek, cut and edit DNA sequences, but the new application works as a sort of alert system. Rather than using the classic Cas9 enzyme, researchers employed a variant called Cas13a (or C2c2) targeting RNAs.  They included a reporter RNA that releases a fluorescent signal when cleaved, and used a technique called recombinase polymerase amplification to further boost sensitivity. As a result they successfully identified specific strains of Zika  in serum, urine, and saliva, as well as dengue virus, pneumonia bacteria and cancer mutations. According to the authors a Sherlock test can be redesigned and synthesized in a matter of days for as low as $0.61/test. Reagents can be lyophilized for long-term storage with no cold-chain infrastructure needed and readily reconstituted for field applications. CRISPR’s potential for diagnostics was made clear last May by a paper published by Mit and Harvard reasearchers in Cell. Other groups are entering the field now, including the company founded by Jennifer Doudna, who contributed to the invention of CRISPR together with Emmanuelle Charpentier in 2012 and is involved in a patent litigation with Zhang.

Broad Institute member Jim Collins explains what SHERLOCK is (video1); Broad Institute core member Feng Zhang explains how CRISPR can be used to detect and diagnose disease (video 2) (Credit: Broad Institute of MIT and Harvard)

 

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