New paradigms in antimicrobial therapeutic development are urgently needed to fight the rapid increase in antibiotic resistance. A variety of Gram-negative human pathogens are becoming increasingly resistant to multiple classes of antibiotics making treatment difficult. This is particularly true for hosts that suffer from chronic infections, such as in those with cystic fibrosis (CF). We’ve partnered with Sarepta Therapeutics to utilize novel antisense technologies to target increasingly resistant gram-negative pathogens. Specifically, we utilize peptide-conjugated phosphorodiamidate morpholino oligomers (PPMOs) to target Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Burkholderia cepacia complex (BCC), and Pseudomonas aeruginosa. We’ve demonstrated successful inhibition of many Gram-negative bacteria by targeting essential, virulence, and antibiotic resistant genes both in vitro and in vivo, and we continue to expand our targets.