Grant: Project Grant

Bacterial infections such as pneumonia, life-threatening infection (sepsis), and other severe infections, are leading causes of mortality worldwide and cause of death by complicating other conditions. Current treatments for bacterial infections are primarily antibiotics that kill "bugs" called bacteria. However, antibiotic-resistant bugs ("super bugs") are losing benefit quickly due to the spread of antibiotic resistance, so we need new, better treatment. One new treatment possibility is to increase the body's ability to remove (clear) toxins of the bacteria, a strategy that complements bacterial killing by antibiotics and is effective even in infections by "super bugs"). Some specific genetic variants decrease the ability to clear toxins. Interestingly we showed that patients with defective genes ("loss-of-function") have higher survival from severe infections (i.e., pneumonia and sepsis). Here, we aim to develop drugs that mimic these loss-of-function genetic variants by developing next generation drugs called "lipid nanoparticle (LNP) RNA-based drugs" that silence genes (by RNA interference) or increase production of helpful proteins by (mRNA), all designed to increase toxin clearance. These drugs would complement antibiotics for treatment of severe bacterial infections. As a commercialization grant, the end goal is to generate enough preliminary proof from studies (proof-of-concept) in animals to demonstrate that these drugs improve patient-centered outcomes (such as survival). Inventions can be patented (IP) and then transferred ("licensed") to a company called Resolve Nanotherapeutics, that will drive clinical development of these urgently-needed drugs for severe infections.