North Carolina-based company Locus Biosciences is pioneering a new approach to combat antibiotic resistance by combining bacteriophages and Crispr technology. Bacteriophages, or phages for short, are tiny viruses that naturally infect and kill bacteria. Locus Biosciences is enhancing the killing ability of phages by equipping them with the gene-editing tool Crispr. The company’s experimental treatment is being tested against urinary tract infections (UTIs) caused by E. coli bacteria.
Phages have the advantage of being selective in the strains or species of bacteria they target, unlike antibiotics that kill bacteria indiscriminately. Although phages were discovered over a century ago and used as medical treatments in the early 20th century, they fell out of use with the advent of antibiotics. However, the rise of antibiotic resistance has renewed interest in phage therapy.
Locus Biosciences has developed a cocktail of six phages, three of which are “lytic” and cause E. coli cells to burst open upon infection. The other three phages are engineered to contain Crispr, which enhances their effectiveness. Once inside the target cells, these phages use the Crispr system to degrade the bacteria’s DNA. A small Phase 2 trial involving 16 women with UTIs showed promising results, with rapid decline in E. coli levels and clearance of UTI symptoms.
The therapy is being co-developed with the Biomedical Advanced Research and Development Authority (BARDA), part of the US Department of Health and Human Services. UTIs are highly prevalent, with more than 80% of infections caused by E. coli. The World Health Organization has reported reduced susceptibility to standard antibiotics in E. coli infections. While phage therapy is licensed in some countries, it is still experimental in the US, requiring permission from the US Food and Drug Administration.
Scaling up phage therapy presents challenges as it is often personalized to individual patients. However, Locus Biosciences’ fixed cocktail approach could facilitate easier scalability. The addition of Crispr to the phages also bypasses mechanisms by which bacteria can become resistant to phages, potentially leading to more effective treatment.
Although the trial results are promising, some experts raise concerns about the convenience and acceptance of the therapy by patients. The current administration of the phage cocktail via a catheter inserted into the bladder may be uncomfortable for UTI patients. Locus Biosciences intends to work on more user-friendly formulations and dosing, such as pills or drinkable liquids. The ongoing second part of the trial will include a control group receiving only the antibiotic Bactrim, allowing for a comparison of efficacy between the phage cocktail and Bactrim alone.