Grant: Project Grant

Factor VII deficiency is a rare inherited disorder that affects about 1 in 500,000 people and causes serious bleeding issues due to the lack of a crucial blood clotting protein. Current treatments in Canada, including recombinant activated factor VII and plasma-derived factor VII, are costly and require frequent administration because they last only 2-6 hours. Our goal is to develop a longer-lasting, more tolerable treatment for Factor VII deficiency using advanced RNA technology. Messenger RNA (mRNA) gene therapy can use the patient's cells to produce Factor VII, reducing the need for frequent treatments. Self-amplifying RNA (saRNA) is a more potent type of mRNA that replicates within cells, requiring much lower doses and lasting much longer than traditional mRNA. We hypothesize that engineering saRNA with improved lipid nanoparticle (LNP) formulations will create longer-lasting, more affordable treatments for Factor VII deficiency. We will create saRNA molecules encoding Factor VII using different viral components, and study their behavior in the body, including duration, replication and protein production. We will develop LNPs-containing drugs to modulate the immune response and test their properties and effects on the immune system. Finally, we will evaluate the safety and efficacy of our saRNA LNP treatments in an animal model of Factor VII deficiency. This research is a collaboration between experts in saRNA therapies at the Blakney Lab at the University of British Columbia and experts in blood disorder treatments at the Kastrup Lab at the Versiti Blood Research Institute. Our work aims to provide a new, effective treatment for Factor VII deficiency with improved dosing, safety and affordability. Additionally, our findings will establish a platform technology that can be adapted to treat other blood disorders and rare genetic diseases.