Antibiotic resistance is one of the biggest potential threats to global health today. But Locus Biosciences is hoping that their crPhage technology might provide a new solution.
Based in North Carolina’s Research Triangle, the startup recently announced promising phase 1b clinical trial results for their use of CRISPR-Cas3-enhanced bacteriophages as a treatment for urinary tract infections caused by escherichia coli. Led in part by former Patheon executive and current Locus CEO Paul Garofolo, the startup launched in 2015 with the goal of using a less popular application of CRISPR technology to address growing antimicrobial resistance.
CRISPR-Cas3 technology has notably different mechanisms from its more well-known CRISPR-Cas9 counterpart. Where the Cas9 enzyme has the ability to cleanly cut through a piece of DNA like a pair of scissors, Garofolo describes Cas3 more like a Pac-Man, shredding the DNA as it moves along a strand.
“You wouldn’t be able to use it for most of the editing platforms people were after,” he said, noting that meant there wouldn’t be as much competition around Cas3. “So I knew it would be protected for some time, and that we could keep it quiet.”
Garofolo and his team wanted to use CRISPR-Cas3 not to edit harmful bacteria found in the body, but to destroy it. To do this, they took the DNA-shredding mechanism of Cas3 and used it to enhance bacteriophages — viruses that can attack and kill different species of bacteria. Together, co-founder and Chief Scientific Officer Dave Ousterout — who has a PhD in biomedical engineering from Duke — thinks this technology offers an extremely direct and targeted way of killing bacteria.
“We armed the phages with this Cas3 system that attacks E. coli, and that sort of dual mechanism of action is what comes together, essentially, as a really potent way to remove just E. coli,” he said in an interview.