CRISPR Diagnostics Could Detect Any Disease on a Paper Strip

As the go-to swiss army knife of gene editing, CRISPR-Cas9 technology has shown promise as an invaluable research tool in cutting-edge genetics. Now, a new company launch signals CRISPR’s latest role as a diagnostics platform that could change the face of multiple industries, and which could make tests for viruses and other diseases as easy as using a pregnancy test.

That diagnostics platform is announced today (April 26th) by newly-launched Mammoth Biosciences, a company that features an impressive list of board members from UC Berkeley and Stanford, boasts support by major investors, and is backed up by central figures in the CRISPR field.

The technology itself involves only a simple modification to the basic CRISPR editing process, says Trevor Martin, Mammoth CEO and Stanford PhD. “I usually think of CRISPR as a ‘search engine for biology’. As when you go into Google and type in a search string to find things for you, with CRISPR you have this thing called a guide RNA, which can also be represented as a string of letters. That’s what tells the CRISPR protein what to go out and find. When you are gene editing, you tell it to go out and find part of the genome to edit. When we are using it for detecting things, we program it to look at unique sequences. Say you want to detect malaria. You find some unique part of the malaria genome sequence that uniquely barcodes the malaria and then once you design that guide that is targeted to that unique malaria barcode the CRISPR protein will go out and find that sequence.”

This video, provided by Mammoth Biosciences, outlines how their diagnostics platform harnesses CRISPR technology.

The changes that the diagnostic platform makes are subtle, but immensely useful, says Martin: “The next step is the same that is used in gene editing - the enzyme will then cut the nucleic acid. Our protein does that as well, but then what we do is leverage this unique property of our protein which is conditional on having found that malaria barcode. It activates this collateral cleavage activity, where not only does the protein cut the sequence that it has found but also cuts orders of magnitude more sequences in the surrounding solution - an amplification, basically. So, we can leverage that by adding this other thing called a reporter molecule in the solution. There are tons of these in the solution with the CRISPR protein and when the CRISPR proteins cleave these molecules, they release a color - that’s how you can actually identify the presence of malaria. So, the entire system, to zoom back out, is the CRISPR molecule with a guide RNA and these reporter molecules, which is a very simple system.” 

The system is so simple, in fact, that it could easily move beyond the confines of a lab setting, and could even have a role as an at-home DIY test, as Martin explains: “Our vision for how the at-home test will work is that you have the CRISPR technology on paper, similar to a pregnancy test. The exciting part about the detection tech is that it can be really used in many different forms. You can imagine using it on paper, or as a more traditional vial-based format, you can maybe even think about putting it in cloth or clothing.” After the at-home test has been run, the patient would simply upload an anonymous photo of the paper test to a linked app, which would fire out results and professional advice within an hour.

The system has the ability to target any DNA or RNA sequence that has been identified, and whilst that makes it immensely powerful as a disease diagnostics tool, it also has implications for other fields: “What we have is a world-class system for detecting DNA and RNA and that means that there is a really amazing application in healthcare but there are also many cases where you want to detect DNA and RNA in fields like agriculture. What if you wanted to know, for example, the microbiome content of some soil or in industry, you wanted to know the microbes in your pipeline or in forensics, you want to DNA-type someone? Really anywhere where you are interested in nucleic acids like DNA and RNA there is a potential use for the system. “

The platform’s potential is matched by the heavyweight backing Mammoth has acquired. Jennifer Doudna, a Professor in both Chemistry and Chemical Engineering, and Biochemistry and Molecular Biology at the University of California, Berkeley, is one of Mammoth’s co-founders, Chair of Mammoth’s Scientific Advisory Board and a hugely influential figure in CRISPR research. “Mammoth’s technology exemplifies some of the most urgent, impactful, and untapped potential in the CRISPR space,” says Doudna. “With use cases ranging from individuals to larger healthcare systems, agriculture, mining, and beyond, Mammoth is taking CRISPR out of the lab to create something that is transformative for the general public.

Investors of the project include Mayfield, NFX and 8VC, and with a $45 billion diagnostics market to tap into, the potential of the project is huge. The most significant impact of the platform, however, could be to make the power of CRISPR available to more people than ever before. “Our aim is definitely to increase access to this type of information and democratize access to that kind of biosensing.” Says Martin. “But even beyond healthcare, we’re aiming to build the platform for CRISPR apps and offer the technology across many industries.”

This article utilizes materials provided by Mammoth Biosciences. For further information, please contact the cited source.