Sherlock Biosciences may take the name of its CRISPR-based diagnostics technology, but the company won’t remain elementary.
It’s launching with $35 million and a two-pronged approach to improving the current state of diagnostics, with the goal of creating new tools that “reach further out, where testing isn’t being done today, but should be."
The Cambridge, Massachusetts-based company has licensed two pieces of CRISPR-based technology from Harvard and the Broad Institute, artfully dubbed SHERLOCK and INSPECTR—cribbed from Specific High-sensitivity Enzymatic Reporter unLOCKing, and INternal Splint-Pairing Expression Cassette Translation Reaction, respectively.
Rather than make therapeutic edits to the genome, SHERLOCK checks for the presence of certain nucleic acid sequences, such as a sequence that appears in the Zika virus. SHERLOCK is a Cas13a-based CRISPR system that targets RNA rather than DNA, and does not stop cutting after reaching its intended target. It also cuts any RNA that happens to be nearby, a feature that can be used to provide a clue that the target is present.
The INSPECTR synthetic biology platform produces a similar signal, but does so in a different way. It uses two halves of an expression cassette that bind to complementary sequences on the target nucleic acid. They then fuse to form a strand of DNA that undergoes transcription and translation—that is, from DNA to RNA, which then codes for a protein, such as a fluorescent one that signals the presence of the target.
Working with the two platforms gives Sherlock “multiple shots on goal,” and allows the company to match its tools to their best application—or even combine the two.
The company describes SHERLOCK as “ultrasensitive,” and needing a little equipment to maintain its temperature. It may be better suited for point-of-care testing in urgent-care facilities or hospital emergency rooms, said Sherlock’s CEO and co-founder, Rahul Dhanda, in an interview.
But INSPECTR is instrument-free and room-temperature stable. It's performed on a paper-based testing system, and could come in handy in the military, consumer health or low-resource areas—much less-finicky diagnostic hardware than was pitched by that other Holmes (Theranos’ Elizabeth).
“Our team has the expertise and technology to transform diagnostics with a powerful set of Engineering Biology tools to enable rapid test design and deployment, an essential component of addressing many healthcare needs, including the growing problem of resistant bacteria,” said co-founder Deborah Hung, M.D., Ph.D., in a statement.
“After early experiments, our tools were quickly used in a wide range of geographies with real patient samples, confirming that we can swiftly respond to urgent healthcare needs,” Hung added.
Licensing both technologies also improves Sherlock’s business prospects: “As we looked out on the landscape ... we came to realize that single-platform companies often get pigeonholed into becoming single-application companies. It’s restrictive in terms of being able to partner because [such companies] are limited to development streams that are built around one particular technology.”
Though part of Sherlock’s $35 million in financing will support “direct product development,” the company is very much focused on developing new applications for its tech through partners.
But it’s keeping its in-house programs a mystery for now, partly because their future depends on which programs Sherlock chooses to team up on. The company said it is fairly deep in those conversations, and could not disclose who those partners will be.
However, more broadly, the company is interested in the “pharmaceutical, diagnostic and nonclinical spaces,” with various applications in oncology, infectious diseases, industrial and home tests, Dhanda said.
Sherlock is launching with a stacked group of co-founders, including CRISPR pioneer Feng Zhang, Ph.D., synthetic biology great Jim Collins, Ph.D., and David Walt, Ph.D., the diagnostics expert who co-founded Illumina. The company has hired a chief technology officer, William Blake, Ph.D., and is looking to add someone to manage partnering and business development, Dhanda said. Other than that, Sherlock plans to grow “fairly rapidly” and bring on “as many scientific staff as possible,” he said.
Sherlock isn’t the only new CRISPR-based diagnostics outfit—last April, Mammoth Biosciences launched with technology licensed from the lab of another CRISPR pioneer, Jennifer Doudna.
Earlier this month, that company added another Cas enzyme to its CRISPR toolbox, expanding the number and variety of diseases it will be able to detect. It is now working with Cas14, as well as Cas12 and Cas13, in its diagnostic platform.