Locus’ treatment is actually a cocktail of six phages. The company uses artificial intelligence to E. coliThree phages are “lytic” and act by infecting. E. coli The phages destroy and burst the cell. The other three are engineered to contain Crispr to enhance their effectiveness. Once inside a target cell, these phages use the Crispr system to target critical sites on the cell. E. coli They sequence the genome and begin to break down the bacteria’s DNA.
Some phages are good at getting into bacterial cells but not so good at killing bacteria, “which is where gene editing comes in,” explains Locus CEO Paul Garofolo. The goal of the treatment, he says, is to “go into the human body and eliminate targeted bacterial species without touching anything else.”
In the Phase 2 trial, 16 women received the phage cocktail for three days along with Bactrim, an antibiotic commonly prescribed for urinary tract infections. Within four hours of the first treatment, E. coli The reduction in urinary uric acid levels was rapid and sustained until the end of the 10-day study period, by which time all participants’ UTI symptoms had subsided and their urinary uric acid levels had declined. E. coli Fourteen of the 16 women had levels low enough to be considered cured.
The findings were reported on August 9th. journal Lancet infectionThe Biomedical Advanced Research and Development Authority (BARDA), part of the U.S. Department of Health and Human Services, is co-developing the treatment.
Urinary tract infections are very common; about half of women will experience a urinary tract infection in their lifetime. More than 80% of infections occur due to E. coli,and 2022 ReportThe World Health Organization estimates that one in five UTI infections E. coli It has reduced susceptibility to standard antibiotics such as ampicillin, cotrimoxazole, and fluoroquinolones.
Phage therapy is common in the Republic of Georgia and Poland but is not approved in the United States. However, it has been used experimentally in certain cases with permission from the US Food and Drug Administration. A major challenge in commercializing phage therapy is that it is often customized for each patient and is difficult to scale up. Finding the right phages for a treatment is time-consuming, and then batches of phages need to be cultured and purified. However, using a fixed cocktail like Locus makes it easier to scale up the therapy.
And there’s another potential benefit: “CRISPR-enhanced phages would allow for the degradation of bacterial genomes, circumventing some of the mechanisms by which bacteria 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 Locus Therapy. “In theory, this could prevent regrowth of phage-resistant bacteria, leading to more effective treatments.”
Photo: Locus Biosciences
