Three Technologies Come Together to Power Sherlock 

Combining CRISPR, synthetic biology and AI to develop a new generation of distributed diagnostic tests. 

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May 2023 – 

Diagnostic tests are vital, but the current system can be challenging. Blood draw sites are often inconvenient, and patients can wait days for results. In addition, people testing for sexually transmitted diseases (STDs), and other potentially sensitive conditions, may opt-out over privacy concerns. 

 

Sherlock Biosciences is working to address these issues by changing how people access diagnostics. The company is developing a suite of sophisticated home tests that provide instant and accurate results.  

 

To get there, Sherlock is leveraging three advanced technologies – CRISPR, synthetic biology and artificial intelligence (AI). By combining these approaches, the company is developing a platform that can replicate results from room-sized, commercial testing equipment in pocket-sized devices.  

 

“Sherlock has created a handheld, molecular testing device that is super accurate, inexpensive to produce and works at room temperature,” said Wouter Meuleman, Partner at Illumina Ventures. “They’ve shown us how CRISPR can be harnessed to decentralize and democratize diagnostics.” 

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The Cas You May Not Know 

Sherlock was founded by David Walt, Ph.D., who co-founded Illumina and other companies and is now a professor at the Wyss Institute at Harvard University; and Jim Collins, Ph.D., a professor of Biological Engineering at MIT and founding faculty at the Wyss Institute. Together, they bring essential expertise in CRISPR, synthetic biology and other disciplines. 

 

Walt, Collins, and their colleagues saw that CRISPR gene editing technology could be applied to diagnostics – it just needed a little creative tweaking. First, CRISPR is generally paired with Cas9, but there are many Cas enzymes, and their activities vary. While they all act like little scissors, cutting targeted DNA sequences, some are more suitable for diagnostics than gene editing. 

 

Cas12 and Cas13 are good examples. These enzymes cleave their targets, but then go rogue, indiscriminately cutting neighboring nucleic acids. That’s a major bug in gene editing, generating abundant off-target cuts, but it’s a feature in diagnostics. 

 

“When we use Cas as a reporter, this collateral activity amplifies the signal,” said Bryan Dechairo, Ph.D., Sherlock’s president and CEO. “The Cas enzyme gives us high specificity, plus this further amplification provides added sensitivity.” 

Amplification at Room Temperature   

Central lab diagnostics machines have the luxury of size, which means they can do things like temperature cycling to amplify genetic material. But at-home devices must work at room temperature, which poses a challenge. 

 

This is where Jim Collins’ synthetic biology chops come through, producing an amplification system that works at ambient temperatures. Called INSPECTR, the platform uses dried, synthetic genes to amplify targets, providing strong readouts without big, expensive instruments.  

 

Once INSPECTR finds the target – which can be virtually any nucleic acid – it generates a reporter protein that can be visualized on a lateral flow strip, like the ones in pregnancy or COVID tests. INSPECTR and CRISPR work exceptionally well together, providing precise results and eliminating data noise.  

 

“When you amplify samples at room temperature, you also amplify molecules you don’t want, which is problematic for ambient temperature diagnostics,” said Dechairo. “But CRISPR cuts through that noise and only signals when the actual target gets amplified, boosting specificity.” 

 

The trifecta piece is AI. Proprietary machine learning algorithms help Sherlock scientists predict the best assays and the most effective CRISPR enzymes, as well as identifying other components, accelerating assay design and product development. 

 

“We’re accustomed to disposable antigen tests, like pregnancy tests, but now we can offer PCR- level accuracy with CRISPR,” said Dechairo. “It’s the same form factor as the low-cost tests we’ve bought for years.” 

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The Advantages of Decentralized Diagnostics 

Sherlock’s COVID test has completed clinical trials and is waiting for FDA 510K clearance. The company is also working on a range of tests for sexual health and respiratory conditions. In addition to being more convenient, these at-home diagnostics could bring the benefits of diagnostic testing to million in rural U.S. communities and developing nations. 

 

“We could bring important tests to low-income countries in sub-Saharan Africa, for example,” said Dechairo. “The price would be low, and they wouldn’t need a central lab to process results –access, affordability and accuracy.”   

 

Sherlock tests could also be ideal for young people who may be concerned about an STD. A home test offers both convenience and privacy.  

 

“When people first get symptoms, or even before symptoms, they’ll be able to detect their condition accurately,” said Dechairo. “This can be particularly important for diseases like chlamydia or gonorrhea, which are becoming more common, and people may not even know they’re sick. People can test themselves, privately, at home, without the potential embarrassment of going to the doctor.” 

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To learn more, visit https://sherlock.bio