Sherlock Biosciences has arrayed a team of all-star academics and innovators in pursuit of next-gen molecular diagnostics. Among its nine co-founders are leading researchers in CRISPR, synthetic biology and genomics pulled from top institutions such as Massachusetts Institute of Technology (MIT), the Broad Institute and the Wyss Institute at Harvard University.

The Cambridge, Mass.-based company is starting off with a pair of in-licensed platform technologies: CRISPR-based Specific High-sensitivity Enzymatic Reporter unLOCKing (SHERLOCK) from the Broad Institute of MIT and Harvard and synthetic biology-driven INternal Splint-Pairing Expression Cassette Translation Reaction (INSPECTR) from Harvard. It has already lined up $35 million, which includes a $17.5 million grant from the Open Philanthropy Project as well as an additional undisclosed equity investment from this nonprofit, which has a mandate to enhance pandemic preparedness.

"On the whole, molecular diagnostics seem really good because they're able to get sensitive results and they're fairly comprehensive today. But there are some performance issues. The other area is the business model around diagnostics, both of which seem to need some innovation. On the performance, as great as the tools are, sometimes they're dependent on processes that take days," Sherlock president and CEO Rahul Dhanda explained to BioWorld. "For infectious diseases, you may not get a result for another two to three days after when you collect the sample. On the oncology side, for instance, the costs are very prohibitive. Some of the testing that's done today are so expensive that not everyone gets a chance to get those results."

"If you think about low-resource settings or decentralized settings, there's not enough simplicity around the platforms to provide results to anybody who needs to be running those tests," he continued. "Separately, there's lots of strong attributes of molecular diagnostics, but in combination none of them are fast enough, sensitive enough and easy enough to be the kind of ubiquitous testing that is important for getting results to anybody who needs them. These two platforms, they're specifically designed to offer rapid sensitive decentralized testing."

Sherlock is in the midst of raising a series A financing; it plans to disclose its total equity investment, as well as its additional major investors, once that process is complete. It's also talking to potential partners across a number of indications and applications with deal announcements anticipated within the next six to 12 months.

Application implications

Molecular diagnostics applications for its platforms are expected to include infectious disease and cancer, with additional work being done on the industrial side as well in agriculture detection and drug bioprocessing. The company expects to partner for several of these efforts, as well as to keep some for in-house development. It expects it could be in the clinic in the life science within the next two to three years.

The idea is to offer easy-to-use, cheap molecular diagnostics that could offer a visual readout and be used in a low-resource setting such as a rural clinic or at home.

"There are a couple of fields in general that are that are probably best addressed. Infectious disease is an area where you know clearly decentralized, rapid sensitive results could have a very big impact on outcomes," said Dhanda. "Oncology, maybe not as rapid but certainly more availability of testing is important and at affordable prices."

Dhanda was previously the SVP of commercial development and marketing at T2 Biosystems, where he helped the company transition from early research to commercial stage.

Sherlock's additional co-founders include CRISPR researcher Omar Abudayyeh of MIT; synthetic biology pioneer James Collins of MIT, Wyss and Broad; cancer genomics specialist Todd Golub of Harvard Medical School; CRISPR researcher Jonathan Gootenberg of MIT; infectious disease expert Deborah Hung of the Broad Institute and Harvard Medical School; computational genomics specialist Pardis Sabeti of Harvard and Broad; David Walt of Wyss and Brigham and Women's Hospital; and CRISPR pioneer Feng Zhang of MIT and Broad.

How it works

On the CRISPR side, relevant research undergirding the company's technology has already been published in a series of four papers published in Science. The SHERLOCK platform uses a means of identifying genetic targets that's based on CRISPR. It can detect genetic fingerprints across multiple organism and sample types.

"It is based on a really cool property of some of the CRISPR enzymes that I and my co-author Omar Abudayyeh data discovered in Feng's lab. CRISPR is really incredible because it's so programmable and very specific. We actually found that some of these enzymes that we discovered, when they actually targeted programmatically to a piece of DNA or RNA depending on the enzyme, they could become activated and start chewing up other things in the solution," said Gootenberg.

He added, "So it's like these kind of bombs, if you will, inside of a test tube. If it found what it was looking for, it was activated and would cut other things. What that allows us to do is, if those other things that are cut are a reporter molecule that we can detect, then we can check those molecules and they can be allowed to run fluorescence tests or even pregnancy-like format tests."

INSPECTR is a synthetic biology-based molecular diagnostics platform. It can be programmed to identify targets based on just a single nucleotide without any instrumentation and at room temperature.

"On their own, they are discreetly powerful. There are some applications where one might want one platform versus the other. That's the versatility of having multi-platforms. We're in discussions with partners, including some want to be home testing without instrumentation. INSPECTR fits beautifully there," said Dhanda.

"There are others who want ultra-sensitivity at the emergency room for potential pathogens. SHERLOCK fits beautifully there," he concluded. "There will be applications where we're either could satisfy ... There is some concept of joining the two platforms and that may put the benefits of both into a single approach. But it's early on that and there's work to be done."

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