Mammoth Biosciences Comes out of Stealth Mode to Use CRISPR Tech to Diagnose Diseases

Mammoth Biosciences, based in San Francisco, has officially launched to develop CRISPR technology for clinical diagnostics. The company was co-founded by two Stanford PhDs, Trevor Martin, chief executive officer, and Ashley Tehranchi, chief technology officer, and two Berkley PhD students, Janice Chen and Lucas Harrington, and Jennifer Doudna, who originally co-discovered CRISPR gene-editing technology.

CRISPR is a gene-editing technique that allows researchers to quickly and precisely edit DNA. In drug development, it utilizes a bacterial protein called Cas9. CRISPR Therapeutics, one of the earliest companies based on the technology, is expected to begin human clinical trials in Europe for beta thalassemia, a blood disorder that decreases the production of hemoglobin. China has several ongoing clinical trials for various diseases using CRISPR. In the U.S., there is only one, at the University of Pennsylvania for melanoma, sarcoma, and multiple myeloma.

Mammoth, however, is not a drug development company. The company is attempting to develop point-of-care diagnostic tests by using CRISPR. Wired speculates that Mammoth is likely to use Cas12a, formerly known as Cpf1. Doudna, Chen and Harrington published a paper in the journal Science in February that showed how Cas12a could identify different strains of human papillomavirus in human samples. Martin told The Verge that Cas13a was also of interest.

Both Cas9 and Cas12a attach to a DNA strand when it reaches its target and cuts. But what Cas12a then does is different. As Wired notes, "It starts shredding up any single-stranded DNA it finds."

In the paper, Doudna and her team describe how they programmed Cas12a to shred two strains of HPV that can cause cancer. Then they added it with a "reporter molecule," which is a bit of single-stranded DNA that issues a fluorescent signal when cut, to the test tubes of human cells. Cells infected with HPV glowed. Healthy cell did not glow.

Martin told Wired, "There are these really amazing biosensing properties of CRISPR that people hadn’t realized for a long time. Billions of years of evolution have given us these incredible proteins, which science is just beginning to characterize."

The company raised $120,000 from NFX Guild in 2017. Since then it has raised funds from several sources, including Mayfield, NFX, 8VC, AME Cloud, Wireframe, Kairos and Boom Capital. They have not disclosed the total amount raised.

"Because we have this really transformative platform for disease detection, it’s really allowing us to rethink the business models about building this type of biotech company," Martin told TechCrunch."Because the technology is so programmable, we’re really leveraging [to make] Mammoth a platform company for detection."

Now the company is interested in partnering with universities or corporations that have potential diagnostic biomarkers that can be utilized in its CRISPR program. Martin told TechCrunch, the plan is to use its device-free system "to bring these biomarkers the last mile or even the last foot into the healthcare system. We’re really excited to partner with these companies to use our platform. [Mammoth] enables these awesome biomarkers to actually get used."

Mammoth isn’t the only group working on using CRISPR for diagnostics, and is also possibly a source of potential roadblocks. Feng Zhang and his group at MIT is working on a CRISPR test called SHERLOCK.

Why that’s of particular interest is that Doudna and Zhang have been involved in patent disputesover CRISPR pretty much since the patents were filed. And, for that matter, Zhang also published a paper in the journal Science earlier this year describing his team’s use of CRISPR to detect microorganisms in patient samples, in Zhang’s case, dengue and Zika viruses, as well as lung cancer mutations in DNA.

Doudna and Emmanuelle Charpentier published the first paper describing CRISPR technology in 2012. But Zhang had filed a broad U.S. patent claim on the technology based on laboratory notes to prove he was the first inventor. Charpentier was then at the Max F Perutz Laboratories at the University of Vienna in Austria. At least 10 patents are involved in the various lawsuits, which are still ongoing.

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