The gene editing technology CRISPR, which has already spawned several startups aiming to use the tool to develop new therapies, is now the inspiration for a new company in a less-crowded space: diagnostic testing.
Sherlock Biosciences is launching in Cambridge, Massachusetts with $ 35 million in funding. That includes $ 17.5 million in the form of a non-dilutive grant from the Open Philanthropy Project, an organization primarily funded by billionaire and cofounder of Facebook and Asana Dustin Moskovitz and his spouse Cari Tuna. The Open Philanthropy Project is also making a separate investment in Sherlock, along with other undisclosed investors. CEO Rahul Dhanda says he’s still raising more funding for the company’s Series A.
One of Sherlock Biosciences’ key technologies comes from the Broad Institute lab of Feng Zhang, who did some of the early work elucidating the DNA-modifying potential of CRISPR and its associated enzymes after their discovery in bacteria.
The founders, a long list of scientists including Zhang, Massachusetts Institute of Technology synthetic biologist James Collins, and scientific founder of genome-sequencing giant Illumina David Walt, “came together because we recognized a problem that has to be solved in the diagnostics space,” says Dhanda, namely that getting test results can take too long and testing may not be accessible in low-resource settings like the developing world. The vision: “We can make a difference if we can develop technology and platforms that deliver on the performance of molecular diagnostics necessary to make clinical changes, but also bring cost effectiveness and simplicity to the table.”
The founding team at Sherlock isn’t alone in recognizing an opportunity to use CRISPR to innovate in the field of diagnostic testing. Last year Mammoth Biosciences, a diagnostics-focused CRISPR company with technology licensed from the University of California, Berkeley developed in the lab of early CRISPR researcher Jennifer Doudna, raised $ 23 million from investors including Mayfield, 8VC and Apple CEO Tim Cook.
The University of California, Berkeley and the Broad Institute had been embroiled in a legal dispute over patents covering the original CRISPR gene editing technology with an enzyme called Cas9, though as of last month the U.S. Patent Office has granted patents to both institutions.
Omar Abudayyeh and Jonathan Gootenberg, also Sherlock cofounders, developed the company’s eponymous technology in Zhang’s lab collaborating with Collins. SHERLOCK stands for Specific High sensitivity Enzymatic Reporter unLOCKing and hearkens back to CRISPR’s original purpose in nature as a bacterial immune system to remember viral invaders, recognize them if they return, and fight them by cutting up their genetic material. “We’ve leveraged this search and destroy feature of CRISPR, which has evolved over billions of years to find precise sequences of DNA, to be a diagnostic, essentially finding precise sequences of DNA for disease or for agriculture” says Abudayyeh.
The system recognizes a DNA or RNA sequence the scientists have programmed it to target. Once that happens an enzyme called Cas13 cuts not only the original sequence, but also cuts molecules added to the sample, triggering them to do things like light up. “We have really optimized the system and gotten to the point we can continue to push the parameters that are important for diagnostics, like sensitivity, speed, and accuracy,” Zhang says.
Sherlock Biosciences has also licensed another technology it’s calling INSPECTR, which recognizes DNA or RNA in the same way as SHERLOCK, but has a different mechanism to signal a hit. When the system matches with the DNA or RNA sequence it’s looking for, it’s like two pieces of a puzzle come together, says Collins, who developed the system: “It now allows that puzzle to become a machine that will make a protein,” reporting detection. Collins thinks both INSPECTR and SHERLOCK will be incorporated into handheld devices that can process samples in a few minutes to an hour and provide a result on the spot, like a pregnancy test.
The company isn’t yet disclosing what specific tests it will develop, but the scientific founders mention interest in a diagnostic test that could identify the bacteria or virus behind an infection to inform patient care rapidly. Deborah Hung, co-director of the Infectious Disease and Microbiome Program at the Broad Institute, is another cofounder. A previously published scientific paper on SHERLOCK describes testing the technology to identify mutations causing lung cancer in patient blood samples. CEO Dhanda mentions other potential applications in agriculture, food safety, and quality assurance in manufacturing biological drug products.
Sherlock cofounder Pardis Sabeti’s lab at the Broad Institute has partners field-testing SHERLOCK technology on Lassa fever in Nigeria, dengue in Senegal, and Zika virus in Honduras. Sabeti’s lab is also working on developing a diagnostic test for tick borne infections. “I think the thing that I’m most excited about is you have a technology that reads the genome sequence directly that could be deployed to the field,” Sabeti says. “There hasn’t been a lot of genome based technology that can be deployed on paper.”
Cofounders Abudayyeh and Gootenberg, who were on Forbes’ Healthcare 30 Under 30 list in 2018, considered joining Sherlock Biosciences full-time but instead are staying in academia, opening their own joint lab at the Massachusetts Institute of Technology and advising the company as needed. “SHERLOCK technology taught us how we can study Mother Nature and harness it to create powerful tools for human health and society,” Abudayyeh says, “and I think that’s something we want to keep exploring.”
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