REDUCING THE GLOBAL AMR PATHOGEN BURDEN AND HOSPITAL- ONSET INFECTIONS THROUGH TARGETED CRISPR MEDICINE

The global health threat from AMR bacterial pathogens is eminent and U.S. Centers for Disease Control and Prevention (CDC) recommends population-based pathogen and AMR reduction strategies as an interventional strategy to fight the AMR threat and to reduce hospital-onset AMR infections1. While antibiotics have been successful agents and have shown clinical efficacy in pathogen reduction, the rising resistance threat and the collateral microbiome damage caused by these broad-acting molecules calls for urgent development of precision medicines1. AMR genes are widely transferred horizontally between bacteria, and hence therapeutics with broad and robust applicability but with very specific mode of action are required. SNIPR has developed specific CRISPR mediated targeting of AMR bacterial pathogens. The CRISPR systems can be delivered by broad-host range conjugative plasmids from a live, safe, probiotic bacterial chassis strain to pathogenic target bacteria and remove the AMR genes with- out disturbing the natural microbiota of the gut. Our vision is to repurpose the use of existing, safe and affordable antibiotics globally by removal of AMR genes carried in bacterial pathogens. Target selection is guided by WHO/CDC pathogen priority lists and has a particular focus on AMR genes that can be transferred horizontally. The central project goal is to develop CRISPR medicines that precisely can remove the world’s most problematic AMR genes from the most dangerous bacteria without disturbing the natural microbiome.