First CRISPR-based Drug Targeting E. coli Infections

E. coli infections are often seen as unfavorable and bothersome, and many people have had them. However, there is a chance that the bacteria will enter the bloodstream in some people, such as those with blood cancer. E. coli infections in certain circumstances frequently result in death. Mortality is between 15% and 20%.

The most common treatment for such illnesses is the use of antibiotics, which can have negative side effects on the patient’s microbiome, which is crucial to our physical and mental health. Additionally, if antibiotic resistance issues worsen, such treatments are less effective at treating infections.

An international team of researchers has now developed the first CRISPR-based medication candidate that targets E. coli infections specifically while sparing the microbiome. ‘Engineered phage with antibacterial CRISPR-Cas selectively lower E. coli load in mice’ is the title of a recent research published in Nature Biotechnology that details the progress of the therapeutic candidate to the point where it is prepared for testing on people.

The scientists created four bacterial viruses using a significant amount of synthetic biology that precisely eliminate the undesirable microorganisms.

“We believe that a narrow spectrum drug with these properties could be very useful to cancer patients, among others, who often get serious infections that are difficult to treat with current antibiotics,” says Morten Otto Alexander Sommer, a professor at DTU Biosustain, Co-founder of SNIPR Biome, and lead author of the paper.

The Division of Infectious Diseases at Weill Cornell Medicine (US), JAFRAL (Slovenia), and JMI Laboratories (US) all collaborated on the project.

Modifying phages to attack E. coli
A library of 162 naturally occurring phages (viruses that kill particular bacteria) was screened by the team, which is headquartered mostly at SNIPR Biome. Eight of these phages were discovered to have potential for attacking E. coli. The phages were then improved through gene engineering so that they could better target E. coli.

They developed SNIPR001, a cocktail of four of these phages that outperformed naturally occurring phages in their ability to target bacteria in biofilms and lower the amount of E. coli. Additionally, they demonstrated that the mixture of phages was well tolerated in the digestive tracts of mice and mini pigs while lowering the emergence of E. coli. The US Food and Drug Administration has given SNIPR001 a Fast-Track designation (expedited evaluation) and it is currently in the clinical development stage.

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