Engineering RNA-based therapeutics for treatment of sepsis and sepsis induced multiple organ dysfunction syndrome

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Worldwide it affects over 30 million people of all ages and results in 5.3 million deaths annually. In Ireland sepsis contributes to 25% of in-hospital deaths and one in five patients diagnosed with sepsis will die from this disease. To date, therapeutic options for sepsis are limited due to the complex nature of this condition and the lack of effective drugs. Current therapy consists of antibiotics, intravenous fluid replacement, and supportive care but further improvement of the outcome of sepsis is likely impossible solely by advancing prevention and disease management.

Identifying pharmacological agents that can improve patient outcome by modifying the disease process is therefore paramount in better treatment of sepsis. Thus far, clinical trials with small molecules and protein based drugs have failed to identify therapeutics, which calls for the development of novel approaches.

The goal of my research is to develop an effective pharmacological intervention for treatment of sepsis and sepsis induced multiple organ dysfunction syndrome (MODS) based on the delivery of new classes of biologic drugs such as short interfering RNA (siRNA) and messenger RNA (mRNA). RNA-based therapeutics grant an unprecedented specificity and control over protein expression. They have also shown tremendous potential to treat various diseases and demonstrated efficacy and safety in clinical trials. Delivery of RNA molecules to relevant cell types poses the major challenge for their broad therapeutic applications. Therefore, as an expert in drug delivery I will develop novel polymers and nano-sized particles to deliver RNA to lungs and kidneys, two major organs at risk of failure during sepsis, and investigate approaches targeting cellular pathways regulating inflammation and immune response in the cells of the vascular and immune system, that have been implicated in the pathology of sepsis.

Award Date
16 May 2019
Award Value
€799,937.32
Principal Investigator
Dr Piotr Kowalski
Host Institution
University College Cork
Scheme
Emerging Investigator Awards Full