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Start-ups pursue precision antibiotics

Snipr Biome recently raised $50 million for CRISPR-based antibiotics, the latest in a string of financings for new ways to kill bacteria

by Ryan Cross
March 14, 2019 | APPEARED IN VOLUME 97, ISSUE 11


Credit: National Institute of Allergy and Infectious Diseases
New therapies are needed to kill antibiotic-resistant bacteria, including methicillin-resistant

As the antibiotic-resistance crisis looms, scientists are looking for new ways to combat superbugs. In response, investors are backing a bevy of companies developing so-called precision antibiotics designed to kill a single species—or even a specific strain—of harmful bacteria, while leaving the harmless and helpful bacteria in our bodies unscathed.

The start-ups are turning to technologies such as CRISPR gene editing, viral-based gene therapy, and antisense oligonucleotides for gene knockdown. Those tools have largely been reserved for treating rare genetic diseases. Companies such as Denmark’s Snipr Biome hope to change that.

“Everyone was focused on the great things you could do with gene editing in mice and men,” says Christian Grøndahl, CEO and cofounder of Snipr, which recently raised $50 million in series A financing. Snipr is applying the principles of CRISPR gene editing to make antibiotics.

CRISPR gene editing uses a bacteria-derived Cas enzyme to cut DNA at a location specified by a guide RNA. Snipr is developing therapies that hijack bacteria’s own Cas enzymes by simply delivering guide RNAs that force the bacteria to destructively chop up genes essential for their survival.

To avoid antibiotic resistance, Snipr will use several guide RNAs to direct the chopping of many genes at once. The guide RNAs will all be encoded into a DNA molecule that will be delivered into bacteria using a charged, synthetic viral particle, much like DNA is packaged in viral shells for gene therapy in humans. “It’s a killing-gene therapy,” Grøndahl says.

The French start-up Eligo Bioscience and the North Carolina start-up Locus Biosciences have been developing CRISPR-based antibiotics as well. “We believe that this selective and precise way of reaching into the body is the future,” Locus CEO Paul Garofolo says.

At least one major drug company agrees. In January, Johnson & Johnson formed a partnership with Locus to develop treatments for respiratory tract infections that combine the CRISPR strategy with bacteriophages, viruses that selectively kill particular strains of bacteria. Locus got $20 million up front and could earn nearly $800 million more.

Another start-up, UK-based Procarta Biosystems, recently raised about $1.7 million to develop antisense oligonucleotides that block the expression of essential genes in bacteria.

In contrast with many traditional small-molecule antibiotics that wipe out good and bad bugs, these techniques all offer unprecedented specificity in killing harmful bacteria. But the price of the treatments could hinder their adoption.

In addition to treating severe infections, many precision-antibiotic companies emphasize, the tools are perfect for modulating the microbiome, which is increasingly implicated in a spectrum of ailments. For instance, the Israel-based bacteriophage start-up BiomX focuses solely on treating more lucrative conditions such as acne, inflammatory bowel disease, and cancer. The firm raised $32 million in series B financing last month.

Snipr and Locus say they remain committed to treating drug-resistant infections, but they are also working on therapies that take out the bad bugs believed to contribute to cancer and autoimmune disease. Grøndahl compares precision antibiotics to precision medicines for cancer. “They both save lives,” he says. “So the market potential is big.”



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