Grant: Project Grant

Sepsis is an exaggerated, systemic, immune response to an infection that often leads to multiple organ failure. It is the most common cause of death in critically ill patients, and over 2 billion dollars is spent every year in Canada on sepsis care. The current standard of care is supportive - antibiotics or antivirals are given to deal with the source of infection, then supportive care is used such as mechanical ventilation and fluid management, which requires (at least) days of bedside care and frequent assessment. There are no treatments for the underlying genetic dysregulation of sepsis, and we aim to change this. The proposed solution's innovation is a therapeutic formulation to supplement beneficial and reduce detrimental microRNAs, which regulate protein synthesis and influence multiple biochemical pathways. The microRNAs will be encapsulated in a lipid nanoparticle to ensure the therapy's efficacy. The in vivo data show that leading microRNAs are anti-inflammatory, anti-microbial and protect organs from injury. In a mouse model for bacterial induced cardiomyopathy, after treatment with microRNAs the infected mice have significantly improved survival - from ~25% to ~80% after 7 days, which is highly promising. Previous work in profiling the genomic response of the host to sepsis enabled the selection of the therapeutic microRNA type to use. This microRNA-nanoparticle technology is currently at TRL4 having shown the efficacy of the therapeutic in vivo. By using materials prepared under good manufacturing practice, including a larger animal model, then further studying the therapeutic characteristics and efficacy at multiple time points post-infection, we will bring the project to TRL5 and TRL6, respectively. Our research will be supported by the Innovations & Partnerships offices of the institutions. NorthMiRs, a strategic partner that will work to develop further the market potential of the proposed therapeutic, is a spin-off from the University of Toronto.