Locus Biosciences CRISPR-Cas3 Trial Data Shows Promise

Addressing Antibiotic Resistance with Innovative Phage Technology

The escalating threat of antibiotic resistance represents a significant challenge to global healthcare. Locus Biosciences is pioneering a novel approach with their crPhage technology, aiming to provide a new therapeutic avenue.

CRISPR-Cas3 Enhanced Bacteriophages for UTI Treatment

Located within North Carolina’s Research Triangle, this startup recently publicized encouraging results from a phase 1b clinical trial. The trial investigated the use of CRISPR-Cas3-enhanced bacteriophages as a treatment for urinary tract infections stemming from Escherichia coli.

Paul Garofolo, the current CEO of Locus Biosciences and a former executive at Patheon, spearheaded the company’s launch in 2015. The initial objective was to leverage a comparatively underutilized CRISPR application to combat the increasing problem of antimicrobial resistance.

How CRISPR-Cas3 Differs from CRISPR-Cas9

CRISPR-Cas3 technology operates through a distinctly different mechanism than the more widely recognized CRISPR-Cas9 system. While Cas9 functions like precise scissors, cleanly cleaving DNA, Garofolo characterizes Cas3 as resembling Pac-Man, progressively dismantling the DNA strand as it traverses it.

“The functionality wouldn’t lend itself to the majority of gene editing applications that were being pursued,” he explained, adding that this limited competition surrounding Cas3. “This allowed for a period of protection and discreet development.”

Destroying, Not Editing, Harmful Bacteria

Garofolo and his team focused on utilizing CRISPR-Cas3 to eradicate detrimental bacteria within the body, rather than modifying them. They integrated the DNA-shredding capability of Cas3 into bacteriophages – viruses capable of attacking and eliminating specific bacterial species.

Co-founder and Chief Scientific Officer Dave Ousterout, holding a PhD in biomedical engineering from Duke University, believes this combination offers a highly targeted and direct method for bacterial elimination. “We equipped the phages with the Cas3 system to specifically target E. coli, creating a dual mechanism that effectively removes only E. coli,” he stated.

Specificity: A Key Advantage

This level of specificity is a characteristic lacking in traditional antibiotics. Instead of solely targeting harmful bacteria, antibiotics broadly eliminate all bacteria encountered. “We often overlook the impact of antibiotics on the beneficial bacteria within our bodies,” Garofolo noted.

However, the precision of Locus Biosciences’ crPhage technology ensures that only the intended bacteria are destroyed, preserving those essential for normal bodily functions.

Safety and Potential Beyond Infections

Beyond its targeted approach, Garofolo and his team anticipate a high degree of safety. Bacteriophages are generally harmless to humans, and the safety profile of CRISPR in human applications is well-documented.

“This represents our core strength,” Garofolo asserted. “We can develop drugs that surpass the potency of existing antibiotics, utilizing phages – arguably the safest delivery method available.”

While initially focused on treating pathogens and infectious diseases, Garofolo envisions potential applications in immunology, oncology, and neurology. “We are discovering that certain bacteria may contribute to cancer development or gut inflammation,” he said.

If researchers can pinpoint the bacteria driving these conditions, Garofolo and Ousterout believe crPhage technology could offer an effective treatment. “If our hypothesis proves correct, this extends beyond infections and antimicrobial resistance, potentially aiding in cancer treatment or delaying the onset of dementia,” Garofolo explained. “It’s fundamentally altering our understanding of the role bacteria play in human health.”

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