Genes conferring antibiotic resistance (AR) in bacteria (blue arrow) are often carried on circular mini-chromosome elements referred to as plasmids. Site-specific cutting of these plasmids using the CRISPR system, which results in destruction of the plasmid, has been used to reduce the incidence of AR by approximately 100 fold. Pro-Active Genetics (Pro-AG) employs a highly efficient cut-and-paste mechanism that inserts a gene cassette (red box) into the gene conferring AR thereby disrupting its function. The Pro-AG donor cassette is flanked with sequences corresponding to its AR target (blue boxes) to initiate the process. Once inserted into an AR target gene, the Pro-AG element copies itself through a self-amplifying mechanism leading to an approximately 100,000-fold reduction in AR bacteria.