Sci­en­tists are har­ness­ing the same tech­nol­o­gy behind the pow­er­ful gene-edit­ing tool CRISPR to devel­op cheap devices that can quick­ly diag­nose infec­tions. These sys­tems, described in new research, have the poten­tial to rev­o­lu­tion­ize how we detect and respond to virus­es like HPV and Zika, espe­cial­ly in devel­op­ing coun­tries.

The new tools, devel­oped by the labs of CRISPR pio­neers Jen­nifer Doud­na and Feng Zhang, are show­cased in two stud­ies pub­lished today in the jour­nal Sci­ence. In one paper, Doudna’s team describes a sys­tem called DETECTR, which can accu­rate­ly iden­ti­fy dif­fer­ent types of the HPV virus in human sam­ples. In the sec­ond paper, Zhang’s team shows an upgrad­ed ver­sion of SHERLOCK — which was shown last year to detect virus­es like Zika and dengue, as well as oth­er harm­ful bac­te­ria — in human sam­ples.

“A new gen­er­a­tion of diag­nos­tics.”

Togeth­er, these two papers prove the enor­mous poten­tial behind dif­fer­ent ver­sions of CRISPR — and not just to edit genomes. “It enables a new gen­er­a­tion of diag­nos­tics that may be more wide­ly avail­able and more cost effec­tive than cur­rent tech­nolo­gies,” says Mitchell O’Connell, assis­tant pro­fes­sor in the Depart­ment of Bio­chem­istry and Bio­physics at the Uni­ver­si­ty of Rochester, who was not involved in either research.

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 edit pieces of the genet­ic code, and are using it to try to cure dis­eases. CRISPR has been used to pre­vent mice from going com­plete­ly deaf, and to edit immune cells of patients with lung can­cer, to help them fight the dis­ease. The gene-edit­ing tool we often hear about is called CRISPR-Cas9, but there are dif­fer­ent types of CRISPR, with dif­fer­ent types of mol­e­c­u­lar scis­sors, or enzymes.

The CRISPR used in the first Sci­ence study is called CRISPR-Cas12a. Doudna’s team dis­cov­ered that when this type of CRISPR snips dou­ble-strand­ed DNA, it does some­thing inter­est­ing: it starts shred­ding sin­gle-strand­ed DNA as well, says study co-author Jan­ice Chen, a fel­low at Doudna’s lab at UC Berke­ley. “That was an unex­pect­ed find­ing,” Chen tells The Verge. “We were instant­ly, ‘This is crazy.’ This opens a whole new avenue for being able to detect DNA sequence.”

“We were instant­ly, ‘This is crazy.’”

So Chen and her col­leagues decid­ed to engi­neer Cas12a into a diag­nos­tic tool, called DETECTR. It works this way: the CRISPR sys­tem is pro­grammed to detect the HPV DNA inside a person’s cells. When CRISPR detects it, it also cuts a “reporter mol­e­cule” with sin­gle-strand­ed DNA that releas­es a flu­o­res­cent sig­nal. So if the cells are infect­ed with HPV, sci­en­tists are able to see the sig­nal and quick­ly diag­nose a patient. For now, DETECTR was test­ed in a tube con­tain­ing DNA from infect­ed human cells, show­ing it could detect HPV16 with 100 per­cent accu­ra­cy, and HPV18 with 92 per­cent accu­ra­cy. Those two HPV types are par­tic­u­lar­ly dan­ger­ous because they can cause can­cer in men and women.

“Cer­tain­ly there are improve­ments to be made, but as far as a proof of prin­ci­ple exper­i­ment we were real­ly excit­ed,” says Chen. Each DETECTR test costs less than one dol­lar and takes about an hour — which is cheap and quick rel­a­tive­ly to oth­er tests. Now, Chen and her team are try­ing to devel­op the right hard­ware that can allow peo­ple to eas­i­ly read that flu­o­res­cent sig­nal. They also want to test if the sys­tem works with oth­er types of human sam­ples, such as blood, sali­va, or urine.

Com­pared to DETECTR, the oth­er diag­nos­tic tool described in the sec­ond Sci­ence paper is a bit clos­er to being deployed in the field. Called SHERLOCK, this sys­tem uses a vari­ety of CRISPR enzymes, includ­ing Cas12a. Last year, Zhang’s team showed that SHERLOCK uses CRISPR-Cas13a to find the genet­ic sequence of Zika, dengue, and sev­er­al oth­er bac­te­ria, as well as the sequences asso­ci­at­ed with a can­cer muta­tion in a vari­ety of human sam­ples, such as sali­va. Now, the team has improved the tool to be 100 times more sen­si­tive and detect mul­ti­ple virus­es — such as Zika and dengue — in one sam­ple simul­ta­ne­ous­ly. It does this by com­bin­ing dif­fer­ent types of CRISPR enzymes, which are unleashed togeth­er to tar­get dis­tinct bits of DNA and RNA, anoth­er of the major bio­log­i­cal mol­e­cules found in all forms of life. Some enzymes also work togeth­er to make the tool more sen­si­tive.

A col­lec­tion of SHERLOCK paper test strips. Pho­to: Zhang lab, Broad Insti­tute of MIT and Har­vard

“The fact that we can put all these dif­fer­ent enzymes into a sin­gle tube and have them not only play nice with each oth­er, but also tell us infor­ma­tion we couldn’t get oth­er­wise — that is real­ly spec­tac­u­lar and it speaks to a lot of the pow­er of bio­chem­istry,” says study co-author Jonathan Gooten­berg, a PhD stu­dent in the Zhang Lab.

SHERLOCK uses flu­o­res­cent sig­nals like DETECTR, but Zhang’s team also devel­oped a paper strip that dis­plays test results for Zika or dengue sim­i­lar to a preg­nan­cy test. That makes it par­tic­u­lar­ly easy to use, because it doesn’t require any spe­cial equip­ment. “In a dis­as­ter sit­u­a­tion, where you don’t have resources like elec­tric­i­ty… this can be shipped and be done in the spot,” O’Connell tells The Verge. “You don’t real­ly need any­thing, just the sam­ple.” And it’s cheap too: the SHERLOCK paper strips cost only a cou­ple of dol­lars.

Both DETECTR and SHERLOCK need more work. Researchers have to make sure that these sys­tems are incred­i­bly accu­rate before they’re used with actu­al patients. But for devel­op­ing coun­tries that lack state-of-the-art equip­ment and trained per­son­nel, these diag­nos­tic tools could real­ly make a dif­fer­ence. It has “real poten­tial to make an impact on human health and soci­ety,” says study co-author Omar Abu­dayyeh, also a PhD stu­dent in the Zhang Lab.

SHERLOCK paper test strips indi­cate the pres­ence or absence of a tar­get like Zika or dengue virus. Video: Zhang lab, Broad Insti­tute of MIT and Har­vard

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