Crispr-enhanced viruses are used against urinary tract infections

Locus' therapy is actually a cocktail of six phages. The company used artificial intelligence to predict a combination that would be effective against Escherichia coliThree of the phages are “lytic”, meaning they infect Escherichia coli cells and causes them to burst. The other three are engineered to contain Crispr to increase their effectiveness. Once inside their target cells, these phages use the Crispr system to target a crucial site in the Escherichia coli genome and begin to break down the bacteria’s DNA.

Some phages are very good at penetrating bacterial cells but not killing them. “This is where gene editing comes in,” explains Paul Garofolo, CEO of Locus. He says the therapy is designed to “go into the human body and remove a specific type of bacteria without touching anything else.”

In a Phase 2 study, 16 women received a three-day treatment with the phage cocktail together with Bactrim, a commonly prescribed antibiotic for urinary tract infections. Within four hours of the first treatment, levels of Escherichia coli in urine decreased rapidly and remained so until the end of the 10-day study period. At this point, symptoms of urinary tract infection had disappeared in all participants and the levels of Escherichia coli were low enough in 14 of 16 women to be considered cured.

The results were published in the journal on August 9 The Lancet Infectious DiseasesThe Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services, is involved in the development of the therapy.

Urinary tract infections are incredibly common and about half of all women will suffer from a urinary tract infection during their lifetime. More than 80 percent of infections are caused by Escherichia coliand in a 2022 report, the World Health Organization found that one in five urinary tract infections are caused by Escherichia coli showed reduced susceptibility to standard antibiotics such as ampicillin, cotrimoxazole and fluoroquinolones.

While phage therapy is widely used in the Republic of Georgia and Poland, it is not approved in the United States. However, it is used experimentally in certain cases with approval from the U.S. Food and Drug Administration. A major challenge in commercializing phage therapy is that it is often tailored to individual patients and therefore difficult to scale. Finding the right phage for treatment can take time, and then batches of phages must be grown and purified. However, with a fixed cocktail like Locus's, the therapy could be more easily scaled up.

And there's another potential benefit. “The CRISPR-enhanced phages allow for the degradation of the bacterial genome and would bypass several mechanisms by which bacteria can become resistant to phages,” says Saima Aslam, a professor of medicine at the University of California, San Diego, who studies phages but is not involved in the development of the locus therapy. “In theory, this could prevent the regrowth of phage-resistant bacteria, thus leading to a more effective treatment.”