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CRISPR’s next target: The bad bugs in your gut

The French biotech Eligo Biosciences lands $20 million in series A funding to advance its CRISPR-packed phage platform

by Ryan Cross
September 26, 2017

Credit: Eligo Bioscience
Duportet and Eligo cofounder David Bikard.
Credit: Eligo Bioscience
Duportet and Eligo cofounder David Bikard.

Doctors may one day prescribe pills filled with the CRISPR gene-editing system to seek and destroy the DNA of bad bugs that create disarray in the microbiome or are resistant to antibiotics.

This idea is about to be tested thanks to a $20 million series A funding round from Khosla Ventures and Seventure Partners for Eligo Bioscience, a French biotech firm aiming to develop and commercialize the concept.

The CRISPR/Cas9 gene editing system gets attention mostly for its pervasive use in research, its ongoing development by multiple companies as a therapy to treat genetic diseases, and its recent controversial use in the editing of human embryos.

But Eligo has a different use for CRISPR in mind. Xavier Duportet, a synthetic biologist and Eligo’s CEO, says the firm is designing virus-derived “nanobots” to unleash CRISPR’s molecular scissors on disease-causing bacteria while permitting other gut microbe residents to live in peace.

Both when used as a gene-editing tool and as a potential therapy, CRISPR contains two components: a Cas enzyme that cuts DNA, and a RNA strand that directs the enzyme to a specific and complementary strand of DNA for cutting. Eligo scientists are stripping down bacteria-infecting viruses, called bacteriophages, to their hollow shells and filling the payload with CRISPR. The modified bacteriophage shuttles its CRISPR cargo into bacteria, where it chops carefully selected strands of DNA essential for cell survival and causes the bugs to die.

“CRISPR is hot, and it works great. But what’s hard is delivery,” Duportet says. He thinks Eligo has an advantage over the delivery platforms (such as adeno-associated viruses and lipid nanoparticles) that other companies plan to use for getting CRISPR into human cells for therapeutic gene editing. Eligo’s therapy only has to be delivered to the gut, meaning it could be ingested in a pill, and the firm says it doesn’t have to worry about off-target cuts from CRISPR in human DNA, since bacteriophages only infect bacteria.

Eligo’s first therapy in development is for an unspecified “rare disease caused by a gut bacteria for which there are not current treatments available,” Duportet says. The new funding is expected to get the therapy through development, Phase I clinical studies, and possibly Phase II clinical studies. He plans to start trials by 2020.

Using CRISPR as an antibiotic or microbiome modulator has mostly remained under the radar since Eligo’s founding in 2014. Today’s announcement represents the first significant funding for the idea. Another start-up called Locus Biosciences, based in Research Triangle Park, N.C., is similarly using CRISPR-filled bacteriophages to selectively kill bacteria.

Duportet emphasizes that his vision for Eligo’s technology is as more than just a bacteria killer. His team is exploring other ways to use the CRISPR-filled viral shells for treating diseases. Duportet acknowledges the new technology may seem financially risky. “But if it works, it could become a cornerstone of personalized medicine,” he says.

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