CRISPR goes Mammoth

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The gene-editing tool CRISPR is moving toward the market, promising better tests, disease cures — and maybe even a woolly mammoth.

The big picture: CRISPR is already a historic scientific achievement, but we're just now entering the moment when it will begin to impact patients and possibly the planet.

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Driving the news: The San Francisco-based CRISPR startup Mammoth Biosciences — whose co-founder Jennifer Doudna shared a Nobel Prize for chemistry last year for her role in discovering the gene-editing tool — announced $195 million in funding late last week, valuing it at more than $1 billion.

  • "The fundamental platform we're building at Mammoth is using CRISPR as a toolbox system" for diagnostics and treatments, says Trevor Martin, Mammoth's co-founder and CEO.

How it works: CRISPR — which stands for Clustered Regularly Interspaced Short Palindromic Repeats — are bits of genetic code that bacteria have evolved to locate and destroy viruses.

  • Mammoth first focused on using the tool to develop diagnostic tests for diseases by programming CRISPR sequences to seek out a particular stretch of RNA or DNA in a virus.

  • The relative ease of programming CRISPR opens up the possibility of cheap and accurate tests that could diagnose multiple pathogens simultaneously — one reason why the company received funding from the Defense Department in January to develop a point-of-care test that could detect up to 10 pathogens at once, as well as a larger, lab-based test that could detect up to 1,000.

  • Mammoth has also received funding from the NIH to scale up a disposable, handheld COVID-19 test.

What they're saying: Right now with COVID tests, "you have to decide whether you want a highly accurate test that might take a while, or do you want to be really easy and accessible, but not as reliable," says Martin.

  • CRISPR-enabled COVID tests that offer both speed and reliability "are the long-term promise of CRISPR diagnostics," he adds.

Between the lines: The first and most widely known CRISPR enzyme is called Cas9, but Mammoth has also been developing new enzymes like Cas12, Cas13 and Cas14.

  • These enzymes are as little as a third the size of Cas9, which means they can reduce unwanted off-target effects during treatments and can be more easily delivered to the body via viruses or nanoparticles.

  • These new CRISPR enzymes have been patented by Mammoth, which helps them avoid a patent battle like the one the University of California-Berkeley (where Doudna works) and MIT’s Broad Institute fought to determine who owns the rights to the original Cas9.

What to watch: Another new company wants to use gene editing for an even more audacious goal: bringing back an extinct animal.

  • This week the startup Colossal launched with the plan to use CRISPR to add 60-plus genes from the extinct wooly mammoth into the cells of an embryo of an Asian elephant, the mammoth's closest living relative.

  • If Colossal succeeds, it plans to reintroduce the re-engineered mammoths to their original habitat in Siberia, which the company's co-founder, Harvard geneticist and CRISPR pioneer George Church, has argued could help reduce the release of CO2 from the rapidly warming tundra.

The catch: Colossal faces major scientific challenges — including building an artificial womb that can gestate a 200 lb. hybrid mammoth fetus — as well as ethical questions about whether it's humane to bring back and set loose a long-extinct animal.

  • Yes, but: Gene editing could emerge as a powerful tool for conservation by allowing scientists to edit endangered species to better resist pathogens or adapt to a changing climate.

The bottom line: CRISPR is poised to fundamentally change both humans and other species, which means that "we as a society have to actually choose what we want to do," says Martin.

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