Broad-spectrum antibiotics are like nuclear bombs, annihilating all prokaryotes they come across.It’s certainly effective at eliminating pathogens, but not so great at maintaining a healthy microbiome. We need precision antimicrobials that can be ignored and let them thrive. SNIPR biome, is a Danish company founded to do just that. His first drug, SNIPR001, is now in clinical trials.
The drug is designed for cancer patients with blood cell involvement. The chemotherapy these patients require can cause immunosuppression along with increased intestinal permeability, so it cannot fight off infections that may be acquired from bacteria escaping from the intestine into the bloodstream. Mortality from such infections in these patients is approximately 15-20%. Many of the infections are Escherichia coliand many of these Escherichia coli It is already resistant to fluoroquinolones, antibiotics commonly used to treat these types of infections.
The team at SNIPR BIOME has engineered bacteriophages, viruses that target bacteria, to be hyperselective. They started by screening 162 phages to find phages that were widespread. Escherichia coli Strains taken from the intestines of people with bloodstream and urinary tract infections and healthy people. They settled on a set of eight different phages. They then engineered these phages to carry the genes encoding the CRISPR DNA-editing system and the RNAs needed to edit many essential genes in cells. Escherichia coli genome. This approach has been shown to prevent resistance evolution.
After testing the capacity of these eight engineered phages, Escherichia coli Alone and in combination, the panel determined that those four groups were the most effective and named the mixture SNIPR001. The team confirmed that SNIPR001 was stable in storage for 5 months and did not affect other gut bacteria.
The researchers showed that SNIPR001 was well tolerated. gottingen mini pig— After oral administration, pigs showed no clinical, biochemical, hematological, or immunological effects and no phages were detected in blood, so there was no systemic exposure. Dosing reduced the amount of target Escherichia coli Found in faeces, none recovered Escherichia coli It was resistant to phage cocktail.
Phage therapy, though fascinating in theory, has a checkered history at best. But SNIPR BIOME’s goal of using CRISPR to precisely target only harmful bacteria could revitalize the technology, allowing it to continue to outmaneuver its bacterial foes without promoting drug resistance. There is a possibility.
Nature Biotechnology, 2023. DOIs: 10.1038/s41587-023-01759-y
