Jennifer Doudna Cofounded Mammoth Biosciences Bags $45M for CRISPR Based Diagnostics

By Ruchi Jhonsa, Ph.D.

The San Francisco based startup, Mammoth Biosciences, co-founded by one of the pioneers of the CRISPR technology, Prof. Jennifer Doudna, raised $45 million in Series B funding on Thursday. Launched in 2018 with the mission to diagnose diseases by CRISPR technology, Mammoth plans to funnel the funds into the expansion of the company in the direction of CRISPR based therapeutics and gene editing.

CRISPR Based Diagnostics

Based on the conventional CRISPR technology with some modifications in the Cas machinery, CRISPR based diagnostics detect disease-causing genes quickly and precisely. The CRISPR based disease diagnosis is a two-step process. First, a Cas protein-guide molecule detects the disease gene and cuts it at a defined location. Next, after a specific detection of the target, the Cas protein cuts a reporter molecule in the vicinity and produces a visible color, indicating a positive test result. A negative result is when the Cas protein has not bound to a specific target gene and the color is not generated.

For diagnostic applications, it is important to have a Cas protein that specifically cuts the gene before cutting the reporter. Conventional Cas protein, Cas9 might non-specifically cut reporter before binding to the target thereby generating a false result. Since CRISPR diagnostics cannot rely on conventional Cas9, it is important to find new Cas proteins. At Mammoth, three families of Cas proteins namely Cas12, Cas13 and Cas14, were discovered that work well for diagnostic applications. Out of three Cas families, Cas14 is particularly useful in diagnosis because of its small size and its ability to quickly generate a signal once it finds target DNA in the sample, says Martin, the co-founder. When it comes to gene editing, these properties will enable Mammoth to achieve precise editing with a greater target range for both ex-vivo and in-vivo applications. Looking at the traction that the CRISPR toolkit has already generated, the company will invest a part of the fund in the development of the CRISPR platform with a particular focus on the characterization of Cas14.

Future Implications

Implications of the technology are far-reaching. One of the early partners of the company is Horizon Discovery, a leader in bioproduction that is utilizing CRISPR tools developed at Mammoth to create new tools for editing Chinese hamster ovary cell line. Recently, Mammoth also partnered with UCSF researcher Charles Chiu to create a rapid diagnostic test for the coronavirus that has affected more than 6000 people and killed 259. The current diagnostic method for coronavirus detection takes six or more hours to show positive or negative results. But with the CRISPR based test which is available in an instrument-free disposable format, it will take one to two hours and can be easily performed in a doctor’s clinic says, Chiu. Mammoth is also developing new partnerships with companies to leverage the CRISPR toolkit in gene editing, therapeutics, and diagnostic application.

References
1. https//www.webwire.com/ViewPressRel.asp?aId=254210
2. https://mammoth.bio/2019/06/10/the-cas-proteins-behind-crispr-diagnostics/

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Author

Ruchi Jhonsa