Sherlock Biosciences Files for IPO to Advance Next-Generation CRISPR and Synthetic Biology Diagnostic Platforms

Following a $35 million funding round led by Northpond Ventures and Baidu Venture Capital (BV) in March this year, biological diagnostics company Sherlock Biosciences has secured two additional grants from the Defense Threat Reduction Agency (DTRA) and the Bill & Melinda Gates Foundation over the past two months. These funds will help advance the development of its two technology platforms, SHERLOCK and INSPECTR, laying a solid foundation for new diagnostic applications to enable diagnostics across various general-use scenarios.

This September, Sherlock Biosciences announced that it had received a grant of approximately $2 million from the Defense Threat Reduction Agency (DTRA). The funding will be used to advance rapid diagnostics for pathogens and other biological threats. This two-year grant will help Sherlock Biosciences expand the application of the Sherlock platform in battlefield environments and further refine the platform’s computational tools.

Following last week’s announcement, Sherlock Biosciences has revealed that it has secured funding from the Bill & Melinda Gates Foundation. The grant will support further research and development, with a focus on diagnostic applications for resource-limited settings. The specific amount of the funding was not disclosed.

Sherlock Biosciences’ two technology platforms, SHERLOCK and INSPECTR, have licensed technologies from the Broad Institute and Harvard University, respectively. These platforms encompass a suite of unique patents covering CRISPR and synthetic biology, enabling the development of next-generation molecular diagnostic technologies that are low-cost, rapid, and broadly applicable.

In other words, rather than opting to improve existing diagnostic testing methods, the company is attempting to develop entirely new diagnostic pathways to enable rapid detection of various diseases that are currently not feasible. “We aim to address those conditions that should be subject to rapid testing but for which no such solutions are currently available on the market,” summarized Rahul Dhanda, CEO of Sherlock Biosciences, regarding the potential applications of future novel diagnostic technologies. Therefore, although the company envisions that Sherlock’s optimal testing scenarios would be in physicians’ offices or hospitals, it is entirely possible that its technology will also be deployed in resource-limited or hard-to-access settings such as battlefields and homes in the future.

SHERLOCK(Specific High-sensitivity Enzymatic Reporter unLOCKing, SHERLOCK) is one of the company’s foundational platforms, developed and refined by Feng Zhang’s team at the Broad Institute, and can be used in point-of-care and clinical diagnostics. In April 2018, a team led by Broad Institute researcher Pardis Sabeti successfully demonstrated that SHERLOCK could detect the Zika virus in field settings.

SHERLOCK combines various enzymes from the CRISPR-Cas13 family with Cas12a and Csm6 to enable simultaneous detection of multiple nucleic acids. SHERLOCK also features a paper-based lateral flow strip that allows for visual readout without the need for any external instruments, similar to a home pregnancy test.

Another foundational platform of the companyINSPECTR(INSPECTR, INternal Splint-Pairing Expression Cassette Translation Reaction) is a synthetic biology-based molecular diagnostic system developed under the leadership of Jim Collins at Harvard University’s Wyss Institute. This system can distinguish single-nucleotide targets at room temperature without the need for any instrumentation. INSPECTR consists of DNA hybridization sensors that can be programmed to detect target nucleic acids with single-base-pair specificity, and converts the sensor detection results into bioluminescent signals via a paper-based synthetic gene network.

According to Rahul Dhanda, CEO of Sherlock Biosciences, the funding secured by Sherlock Biosciences will be used to further develop these technologies. The company is also concurrently investing in the research and development of deep learning artificial intelligence technologies to accelerate the development of new diagnostic assays for SHERLOCK and INSPECTR.

“A portion of the funds will be used to design the bioinformatics front-end for detection. The front-end development is highly efficient, enabling us to respond very rapidly to any emerging (biological) threats,” said Rahul Dhanda. “If someone develops a new vector and weaponizes it, our technology can quickly respond to help identify solutions to counteract it.”

Meanwhile, grants from the Bill & Melinda Gates Foundation will primarily be used to develop low-cost, highly accurate, and rapid molecular diagnostic tools that can be deployed in regions prioritized by the foundation, enabling healthcare workers in resource-limited settings to access these advanced disease detection technologies. Rahul Dhanda stated that the Bill & Melinda Gates Foundation maintains a list of target regions, with the aim of facilitating diagnosis and testing in resource-constrained environments.

For Sherlock Biosciences, the primary use of these funds is to advance the SHERLOCK platform and further develop the INSPECTR platform, enabling the technology to be deployed in virtually any setting.

“Broadly speaking, I believe that if ultra-rapid and ultra-sensitive detection is required, we are more likely to use SHERLOCK, as it offers slightly higher sensitivity,” explained Rahul Dhanda. “If testing is conducted in very remote areas where even small, battery-powered point-of-care devices are not feasible, we might opt for INSPECTR instead.”

“Sherlock Biosciences is developing different testing protocols, and the foundation also hopes to use multiple tests to observe multiple markers of the same infection, each of which can diagnose a single type of infectious agent,” said Rahul Dhanda.

Sherlock Biosciences has further developed its SHERLOCK and INSPECTR platforms. For SHERLOCK, researchers are exploring the use of new nucleases to determine which enzymes are effective under specific conditions.

“Most improvements to SHERLOCK have focused on ensuring that each assay performs stably and consistently, enabling us to scale up and subsequently manufacture and develop products appropriately,” added Rahul Dhanda. “We have significantly enhanced performance to ensure it meets the requirements of any assay we conduct and any product we develop.”

As for INSPECTR, William Blake, Chief Technology Officer at Sherlock Biosciences, explained that the company aims to use this platform to bridge the gap between current molecular diagnostic technologies and traditional assays, such as immunoassays, which are straightforward and cost-effective.

“There is currently no other analytical method for detecting nucleic acids that is analogous to immunohistochemistry, so INSPECTR has the potential to become such a platform,” said William Blake. “By converting nucleic acid hybridization into an encoded output—potentially via a reporter that catalyzes a color-changing reaction—antigens can be detected using conventional lateral flow assays. Therefore, we are internally driving this technology toward simple, user-friendly diagnostics that do not require equipment or temperature control, conditions that are currently mandatory for molecular diagnostic techniques.”

William Blake explained, “This technology is built onCell-Free SystemFurthermore, this system enables certain cellular functions to operate normally outside the environment of living cells. Research from the Collins laboratory has demonstrated that cell-free systems are essentially cell extracts that allow functions such as transcription and translation to occur in a homogeneous environment. Moreover, when these cell extracts are lyophilized into porous matrices such as paper, the resulting cell-free systems can be stored at room temperature for over a year while retaining their functional capabilities, including transcription and translation.

“This lays the foundation for the INSPECTR platform, which utilizes cell-free systems that are low-cost, programmable, and can be stabilized via lyophilization for storage at room temperature,” said William Blake. “Combined with innovations in probe design, this enables INSPECTR to assemble nucleic acid sequence probes in response to the presence of a target. When these probe sequences are assembled, they form an expression cassette that can be translated into a pre-encoded output signal within the cell-free system, subsequently catalyzing a colorimetric reaction.”

Moreover, since cell-free systems can remain active over a wide temperature range—a condition under which conventional immunohistochemistry is not feasible—and do not require amplification of the target sequence, this platform enables the development of instrument-free diagnostic technologies using paper or disposable plastics, with products resembling modern pregnancy test strips.

Sherlock Biosciences is also seekingMethod for Integrating SHERLOCK and INSPECTR to Work in SynergyWilliam Blake stated that this combination leverages INSPECTR’s ability to detect nucleic acids at ambient front-end temperatures, along with SHERLOCK’s diverse specialized reaction capabilities at the back end.

“Therefore, by combining technologies and leveraging our CRISPR-Cas-based technical capabilities, we can enable CRISPR-Cas diagnostic systems to achieve high specificity without the need for instrumentation,” added William Blake.

From an application perspective, Sherlock Biosciences is seeking use cases that require centralized, rapid, and highly sensitive performance, with its initial research focus on infectious diseases. However, what makes the company most exciting is its creation of an entirely new diagnostic platform, which distinguishes it from all recently developed testing technologies; the vast majority of such technologies have merely undergone incremental improvements over the past three to four decades.

“Diagnostic tools (in bioengineering) are widely used and powerful, and their introduction has solved problems we once thought unsolvable,” said Rahul Dhanda. “What excites me is that INSPECTR and CRISPR also fall into this category… This allows us to adopt new technologies to solve problems, rather than merely optimizing existing ones. Diagnostics is a distinct field where people have long sought ways to accelerate PCR reaction speeds or use microfluidics to purify samples. In contrast, entirely new platforms leverage these engineered biology tools to directly address all questions, effectively encompassing the very biology we aim to analyze.”

In line with Rahul Dhanda’s thinking, this new diagnostic approach will enable Sherlock Biosciences to conduct diagnostic tests across a variety of settings. He stated, “The new platform allows us to perform DNA testing anywhere in the world today, representing an unprecedented breakthrough.”

For example, physicians can perform infection tests, such as for influenza, on patients in their offices and obtain results rapidly; patients can conduct self-testing at home and then consult with their physicians without leaving their homes. These tools can be used for long-term monitoring of post-treatment outcomes in patients. More importantly, such rapid diagnostic products can be utilized in developing countries.

In fact, the company is researching and developing diagnostic methods for treatment efficacy monitoring. Although this concept is still in its early stages, the technology has the potential to perfectly address patient compliance challenges in tumor recurrence monitoring. Rahul Dhanda stated that Sherlock Biosciences is also in discussions with pharmaceutical companies to apply this diagnostic technology platform to drug development.