Sherlock Biosciences is leveraging the Wyss Institute’s INSPECTR™ technology to create a highly sensitive, nucleic acid-based diagnostic platform that can deliver accurate results rapidly and inexpensively for a vast range of needs in virtually any setting.
Molecular diagnostics is the fastest-growing segment of the global in vitro diagnostics market, but the vast majority of these tests require expensive equipment and supplies, limiting their use to medical facilities. The COVID-19 pandemic dramatically illustrated the need for cheap, readily accessible, accurate diagnostic tests that can be deployed in non-clinical settings to address public health crises. While at-home molecular COVID-19 diagnostic tests were developed with impressive speed, processing these tests requires instrumentation that increases their cost and impacts accessibility. There are also a wide range of human diseases for which consumer-grade diagnostic technology does not exist.
INSPECTR™ is a molecular diagnostic platform that combines freeze-dried synthetic gene networks with cell-free expression systems to create novel biosensors. These biosensors report the presence of a target DNA or RNA molecule in a sample with single-nucleotide accuracy by producing an easily detectable reporter protein. These diagnostic reactions are shelf-stable, can be performed at room temperature, and do not require power or any additional instrumentation. The diagnostic is activated by simple rehydration with an easily obtainable sample such as saliva, blood, or urine, allowing it to be used in low-resource, at-home, and clinical settings.
INSPECTR™ was developed from the freeze-dried, cell-free reaction technology developed in the lab of Wyss Core Faculty member Jim Collins, Ph.D by Collins and former Wyss Entrepreneur-in-Residence William Blake, Ph.D., who is now Chief Technology Officer at Sherlock Biosciences. The freeze-dried, cell-free reaction technology works by creating two different kinds of freeze-dried pellets: one containing molecular “machinery” that cells use to translate DNA and RNA into proteins, the other containing customizable DNA “instructions” that direct the production of any nucleic acid or protein of interest. When the two types of pellets are combined and rehydrated with water, the instructions and machinery together produce the desired biomolecular product without the need for living cells. Among the many potential applications for this on-the-go biomolecule synthesis is diagnostics, in which a “reporter” molecule is produced in the presence of a “target” molecule.
To pursue this idea, Collins and his team used their technology to create a paper-based diagnostic in which their freeze-dried pellets were embedded into strips of ordinary paper to create an inexpensive test that successfully detected the RNA of the Zika and Ebola viruses and reported their presence by changing color. CRISPR-Cas9 was added to the paper-based diagnostic to enable the identification of different strains of Zika, further enhancing the technology’s accuracy and marking the birth of the field of CRISPR-based diagnostics.
The success of pairing INSPECTR™’s easy nucleic acid detection and readout with CRISPR’s high precision for the paper-based diagnostic inspired the launch of startup Sherlock Biosciences in March 2019 to use these two powerful tools to create accurate, low-cost diagnostics.
Sherlock Biosciences is developing both the Wyss Institute’s INSPECTR™ technology and a CRISPR-based tool called SHERLOCK™ co-developed by Collins and colleagues at the Broad Institute of MIT and Harvard. Collins is one of the nine co-founders of the company along with fellow Wyss Core Faculty member David Walt, Ph.D., CRISPR pioneer Feng Zhang, Ph.D., and infectious disease experts Deborah Hung, M.D., Ph.D. and Pardis Sabeti, M.D., Ph.D.
Sherlock launched with initial financing of $35 million, including a $17.5 million non-dilutive grant and additional investment from the Open Philanthropy Project. One month later, it secured a Series A funding round that brought the overall committed capital to approximately $50 million from Northpond Ventures, Baidu Ventures, and others. In October 2019, it partnered with Mologic to develop a suite of rapid and “instrument-free” molecular diagnostics that work without the need for electricity or temperature controls.
When the COVID-19 pandemic struck in early 2020, Sherlock pivoted its focus to SARS-CoV-2 diagnostics and received the FDA’s first-ever emergency use authorization for a CRISPR-based technology with the launch of the Sherlock SARS-CoV-2 test kit. This test can determine whether a patient sample contains the virus in about an hour, and has been deployed worldwide to help end the pandemic through various partnerships from diagnostic companies to the Ministry of Health in Nepal. The company received additional funding from the Open Philanthropy Project and the Bill and Melinda Gates Foundation to advance their INSPECTR™ platform and develop an over-the-counter disposable diagnostic test for SARS-CoV-2. Sherlock was also named one of Fast Company’s Most Innovative Biotechnology Companies of 2021 and honored as a Fast Company 2021 World Changing Ideas Award recipient.