Real-time Assessment of Antimicrobial Concentrations for Personalized Treatment of Infectious Diseases

This project will deliver, in Phase 1, aptamers build from an artificially expanded genetic information system (AEGIS) that bind to at least four of five antimicrobial targets: amphotericin, voriconazole, colistin, gentamicin, and meropenem. These aptamers will be shown in a prototype to bind these targets at relevant concentrations over a relevant dynamic range in 50 L blood samples. In Phase 2, these will be converted into signaling aptamers, which allow visual yes-no readouts to be generated directly from binding. The signal will immediately inform the caregiver whether more antibiotic should be given. This product can be used with a Firebird companion diagnostic that follows treatment progress for target fungal and bacterial pathogens. Most importantly, this project will introduce DARPA to a new disruptive technology, a synthetic biology platform that completes and corrects defects in natural biopolymers, especially DNA and RNA. Developed through DoD basic research investment, these new biopolymers allow diagnostics and therapeutic agents to meet spec unattainable with natural DNA, RNA, and proteins.