Racing CRISPR into Diagnostics.

CRISPR is revolutionising all areas of life sciences. Its flexibility means that CRISPR-based detection can be applied to industries like agriculture, environmental monitoring, biodefense and more.

Now the race is on to get it into diagnostics. This would bring countless benefits including quicker and more accurate results for both infectious and non-infectious disease.

It would also move many areas of diagnostics closer to the point of care (PoC), with heavy-duty machinery, like PCR instrumentation, no longer required. The stability of the CRISPR-Cas protein complexes means they’re easily handled and transported too, which would make CRISPR diagnostics highly accessible.

CRISPR is a segment of DNA comprising of base repeats that are involved in the defence of bacteria immune systems from harmful viruses.  Upon infection, organisms use Cas proteins and guide-RNA to locate the segment and chop-up the DNA.

Now scientists have found that certain CRISPR proteins, Cas12 and Cas13 can provide signals when they cut the DNA - opening up the field of diagnostics to detect the presence of diseases in patient samples.

Two start-ups are now battling to get this to market first: Mammoth Biosciences and Sherlock Biosciences.

The scientists that discovered CRISPR’s potential in diagnostics - Trevor Martin, Janice Chen and Lucas Harrington – are now co-founders of the first runner in this race, Mammoth Biosciences.

This start-up, based in San Francisco, have a very simple goal: to make molecular diagnostics easy, accessible and affordable. Speaking to Ted Tisch, COO at Mammoth, it was clear that this enthusiasm to democratize diagnostics runs throughout the team.

We’re excited to revolutionize global healthcare, building the first CRISPR-based detection platform. CRISPR diagnostic tests are relatively inexpensive, fast and easy-to-use, making them ideal for decentralized environments.”

Ted Tisch, COO at Mammoth Biosciences

Mammoth’s system, the DETECTR, can be used in decentralized environments within hospitals, doctor’s offices or even the home. The aim is for this to be applied in a variety of locations and regions around the world.

Announcing a $23m round of funding in July 2018, led by the Silicon Valley firm Mayfield Partners and multiple venture firms like NFX and 8VC, Mammoth are well-placed for growth.

This investment has allowed their team to develop infrastructure for the CRISPR platform and carry out specific disease detection tests for healthcare applications. This funding has also supported the product through clinical testing, which is still ongoing.

To guide to them to market, Mammoth have a strong Scientific Advisory Board chaired by Jennifer Doudna, featuring infectious disease expert Charles Chui, plus protein engineering expert Dave Savage – among others.

Excited about their advancements on the core technology, Ted told me that they’re now focused on product development, usability design and regulatory efforts.

Joining Mammoth in the race, Sherlock Biosciences are developing an advanced molecular testing platform to offer versatility for diagnostic solutions.

Their SHERLOCK system, for Specific High-sensitivity Enzymatic Reporter unLOCKing, is one of the company’s core diagnostic technologies. This identifies specific sequences of genetic material in a sample using CRISPR Cas13a. This could include genes present in the Zika virus, among other targets.

Meanwhile, their versatile INSPECTR platform, or INternal Splint-Pairing Expression Cassette Translation Reaction, can be programmed to identify targets from a single nucleotide. It can be performed at room temperature on a paper-based system, without specialized laboratory equipment.

Being applied to oncology and infectious disease, Sherlock’s technology is easy-to-use in virtually any setting. It can provide accurate results in just 30 minutes.

Through series A funding, they’ve managed to raise $49m. This has been led by Northpond Ventures and Baidu Ventures, a firm that specializes in AI and data-driven companies. While this funding has partly supported product development, much of their recent efforts have gone toward sealing new research partnerships.

Incorporating AI to their diagnostics is also on Sherlock’s agenda. In support, investors, Baidu, will also offer their expert technical advice, access to cloud-computing resources, data sets for training machine learning systems and annotation staff to help build out the models.

While it’s exciting times for both these two companies, it’ll be a couple of years until we see these tests democratizing diagnostics, giving the public the power of at-home CRISPR diagnostic testing.

Whoever hits the market first, the impact this technology will have on diagnostics and healthcare will be revolutionary.